| Victors ID |
Gene Name |
Sequence Strain (Species/Organism) |
NCBI Gene ID |
NCBI Nucleotide GI |
NCBI Protein GI |
Locus Tag |
Genbank Accession |
Protein Accession |
Protein Name |
Molecule Role |
Molecule Role Annotation |
PMID |
|
|
rbsK from Brucella suis 1330 |
Brucella suis 1330 |
1164441
|
|
23499772
|
BRA0005 |
|
NP_699212.1 |
ribokinase, putative |
Virulence factor |
FUNCTIONAL GROUP: a.a. metabolism, Unkown [Ref6462:Delrue et al., 2004].
FUNCTION: Ribokinase [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Macrophages [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
mgtB from Brucella suis 1330 |
Brucella suis 1330 |
1164473
|
|
23499804
|
BRA0037 |
|
NP_699244.1 |
magnesium ion-transporting ATPase, E1-E2 family |
Virulence factor |
FUNCTIONAL GROUP: Metal acquisition [Ref6462:Delrue et al., 2004].
FUNCTION: Mg2+ uptake [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
nodV from Brucella suis 1330 |
Brucella suis 1330 |
1164477
|
|
23499808
|
BRA0041 |
|
NP_699248.1 |
sensor histidine kinase |
Virulence factor |
FUNCTIONAL GROUP: Regulation [Ref6462:Delrue et al., 2004].
FUNCTION: Histidine kinase [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
gltD from Brucella suis 1330 |
Brucella suis 1330 |
1164492
|
|
23499822
|
BRA0055 |
|
NP_699262.1 |
glutamate synthase subunit beta |
Virulence factor |
MUTATION: gltD encodes the small subunit of glutamate synthase. It is required for B. abortus growth as shown in signature-tagged transposon mutagenesis. It suggests that glutamate may serve as carbon and/or nitrogen sources during growth of B abortus [Ref6463:Hong et al., 2000]. |
10858227
|
|
|
virB11 from Brucella suis 1330 |
Brucella suis 1330 |
1164496
|
|
23499826
|
BRA0059 |
AE014292 |
NP_699266 |
type IV secretion system protein VirB11 |
Virulence factor |
MUTATION: The virB11 mutation experiment confirms that a complete VirB apparatus is required for their secretion [Ref6464:Marchesini et al., 2004]. |
15312849
|
|
|
virB10 |
Brucella suis 1330 |
1164497
|
|
23499827
|
BRA0060 |
AE014292 |
NP_699267 |
type IV secretion system protein VirB10 |
Virulence factor |
MUTATION: Mutants with polar and nonpolar mutations introduced in irB10 showed different behaviors in mice and in the HeLa cell infection assay, suggesting that virB10 per se is necessary for the correct function of this type IV secretion apparatus [Ref6465:Comerci et al., 2001].
A B. abortus virB10 mutant showed a decrease of intracellular live bacteria comparable to that of the wild-type strain until 4 h after infection, indicating that a functional VirB system is not required for the short-term survival of Brucella inside macrophages. At later time points, the number of live virB10 mutants progressively decreased. Hence, the Brucella virB10 strain did not replicate, but rather was killed. Although the virB10 mutants are capable of short-term survival, they can not evade long-term degradation through fusion with lysosomes [Ref6465:Comerci et al., 2001].
B abortus virB1 and virB10 mutants are unable to persist in mouse spleens after i.p. inoculation, suggest that attenuation in the animal model is due to an inability of these strains to grow intracellularly [Ref6465:Comerci et al., 2001].
A B abortus virB10 mutant lost the ability to multiply in HeLa cells and was not recovered from the spleens of infected BALBc mice [Ref6465:Comerci et al., 2001].
The non polar virB10 mutant was able to block the acquisition of cathepsin D, but was not able to translocate to the replication compartment [Ref6465:Comerci et al., 2001].
The virB10 non-polar mutants were capable of avoiding interactions with the endocytic pathway but , diverging to wild-type Brucella, were unable to reach the endoplasmic reticulum to establish their intracellular replication niche and seemed to be recycled to the cell surface [Ref6465:Comerci et al., 2001]. |
11260139
|
|
|
virB9 from Brucella suis 1330 |
Brucella suis 1330 |
1164498
|
|
23499828
|
BRA0061 |
|
NP_699268.1 |
type IV secretion system protein VirB9 |
Virulence factor |
MUTATION: Uptake in the presence or absence of Ca2 and Mg2 did not influence the subsequent intracellular survival of wild-type Brucella, whereas the decrease in the number of surviving virB9 mutant cells was delayed in the absence of Ca2 and Mg2. Possibly two types of adhesion molecules promoted uptake of Brucella, one being Ca2 and Mg2 dependent and the other not, and that both types participate in the uptake of wild-type bacteria but only the latter type participates in the uptake of the virB9 mutant [Ref6466:Gorvel and Moreno, 2002].
Four independent mutants in virB5, virB9 or virB10 were highly attenuated in an in vitro infection model with human macrophages [Ref6466:Gorvel and Moreno, 2002].
The intracellular fate of three virB mutants (virB2, virB4 and virB9) in HeLa cells by immunofluorescence was examined. The three VirB proteins are not necessary for penetration and the inhibition of phago-lysosomal fusion within non-professional phagocytes. Rather, the virB mutants are unable to reach the replicative niche and reside in a membrane -bound vacuole expressing the late endosomal marker, LAMP1, and the sec61beta protein from the ER membrane, proteins that are present in autophagic vesicles originating from the ER [Ref6466:Gorvel and Moreno, 2002].
Attenuated non-polar virB2, virB4, virB8, virB9 and virB10 Brucella mutants are capable of penetrating cells as the same rate as the virulent wild-type Brucella, transit through EEA1 -positive early compartments and then localize in LAMP1-positive compartments at early times of infection [Ref6466:Gorvel and Moreno, 2002]. |
12414149
|
|
|
virB8 from Brucella suis 1330 |
Brucella suis 1330 |
1164499
|
|
23499829
|
BRA0062 |
|
NP_699269.1 |
type IV secretion system protein VirB8 |
Virulence factor |
MUTATION: virB8 mutant was attenuated by a mini-Tn5 transposon mutagenesis [Ref6466:Gorvel and Moreno, 2002]. Attenuated non-polar virB2, virB4, virB8, virB9 and virB10 Brucella mutants are capable of penetrating cells as the same rate as the virulent wild-type Brucella, transit through EEA1-positive early compartments and then localize in LAMP1-positive compartments at early times of infection [Ref6466:Gorvel and Moreno, 2002]. |
12414149
|
|
|
virB6 from Brucella suis 1330 |
Brucella suis 1330 |
1164501
|
|
23499831
|
BRA0064 |
|
NP_699271.1 |
type IV secretion system protein VirB6 |
Virulence factor |
MUTATION: B. abortus virB6 is essential for intracellular growth within HeLa cells as shown from a mutagenesis study. |
|
|
|
virB5 from Brucella suis 1330 |
Brucella suis 1330 |
1164502
|
|
23499832
|
BRA0065 |
|
NP_699272.1 |
type IV secretion system protein VirB5 |
Virulence factor |
MUTATION: A comparison of the VirB8 and VirB5 contents after induction of the B suis wild type and of virB5 and virB12 mutants further confirmed that the virB5 and virB12 genes belong to the same operon [Ref6467:O'Callaghan et al., 1999].
Smooth strains of Brucella unable to replicate (ie, killed B suis or the avirulent mutant B suis virB5) exhibit delayed phagosome-lysosome fusion [Ref6467:O'Callaghan et al., 1999].
Polar mutations in the operon upstream of virB5 exert a greater effect on the expression of virB5 than they do on the expression of the downstream gene virB12. It indicates that in B abortus , regulatory elements other than the virB promoter may influence VirB12 protein levels [Ref6467:O'Callaghan et al., 1999].
Four independent mutants in virB5, virB9 or virB10 were highly attenuated in an in vitro infection model with human macrophages [Ref6467:O'Callaghan et al., 1999]. |
10510235
|
|
|
virB4 from Brucella suis 1330 |
Brucella suis 1330 |
1164503
|
|
23499833
|
BRA0066 |
|
NP_699273.1 |
type IV secretion system protein VirB4 |
Virulence factor |
MUTATION: A mutant strain of B abortus that contains an in-frame deletion in virB4 is unable to replicate in macrophages and survives in mice [Ref6468:Kim et al., 2004]. ntracellular replication was inhibited in wild-type B abortus after introducing a plasmid expressing a mutant VirB4 altered in the NTP -binding region. VirB4 containing the intact NTP -binding region is essential for evasion of fusion with lysosomes (11988518).
The ruffling associated with internalization of the virB4 mutant results in a more rapid uptake than for the wild-type strain. The virB4 mutant shows primarily small regions of phalloidin staining at the sites of binding. Macrophages incubated simultaneously with B abortus and the fluid-phase marker tetramethyl rhodamine isothiocyanate (TRITC)-dextran accumulate the marker in large vacuoles containing the wild-type strain, but little or no marker accumulates in phagosomes containing the virB4 mutant. Similarly, phase-contrast micrographs have shown the wild-type strain in large phase-transparent compartments, but the virB4 mutant is in much smaller compartments (14738898).
Intracellular growth-defective virB4 mutant and attenuated vaccine strain S19 did not induce abortion [Ref6468:Kim et al., 2004].
The B abortus virB4 mutant was completely cleared from the spleens of mice after 4 weeks, while the pncA mutant showed a 1.5-log reduction of the number of bacteria isolated from spleens after 10 weeks. Splenomegaly was not observed at all in mice infected with virB4 mutant [Ref6468:Kim et al., 2004]. |
15135535
|
|
|
virB3 from Brucella suis 1330 |
Brucella suis 1330 |
1164504
|
|
23499834
|
BRA0067 |
|
NP_699274.1 |
type IV secretion system protein VirB3 |
Virulence factor |
MUTATION: The B abortus virB3 gene is found to be essential for intracellular growth inside HeLa cells [Ref6469:Kim et al., 2003]. |
12761078
|
|
|
virB2 from Brucella suis 1330 |
Brucella suis 1330 |
1164505
|
|
23499835
|
BRA0068 |
|
NP_699275.1 |
type IV secretion system protein VirB2 |
Virulence factor |
MUTATION: The Brucella abortus virB operon, encoding a type IV secretion system (T4SS), is required for intracellular replication and persistent infection in the mouse model. The products of the first two genes of the virB operon, virB1 and virB2, are predicted to be localized at the bacterial surface. Both mutants were shown to be nonpolar, as demonstrated by their ability to express the downstream gene virB5 during stationary phase of growth in vitro. Both VirB1 and VirB2 were essential for intracellular replication in J774 macrophages. The nonpolar virB2 mutant was unable to cause persistent infection in the mouse model, demonstrating the essential role of VirB2 in the function of the T4SS apparatus during infection [Ref6470:Sun et al., 2005].
Polar mutations in the virB1 to virB2 intergenic region or in virB2 reduced the detection of VirB5 to a greater extent than they did that of VirB12. A virB1 mutation also eliminates the transcription of virB12 in B suis [Ref6470:Sun et al., 2005]. |
16113325
|
|
|
virB1 |
Brucella suis 1330 |
1164506
|
|
23499836
|
BRA0069 |
AE014292 |
NP_699276 |
type IV secretion system protein VirB1 |
Virulence factor |
MUTATION: The Brucella abortus virB operon, encoding a type IV secretion system (T4SS), is required for intracellular replication and persistent infection in the mouse model. The products of the first two genes of the virB operon, virB1 and virB2, are predicted to be localized at the bacterial surface. Both mutants were shown to be nonpolar, as demonstrated by their ability to express the downstream gene virB5 during stationary phase of growth in vitro. Both VirB1 and VirB2 were essential for intracellular replication in J774 macrophages. The nonpolar virB1 mutant persisted at wild-type levels, showing that the function of VirB1 is dispensable in the mouse model of persistent infection [Ref6471:Höppner et al., 2005].
A B abortus polar virB1 mutant failed to replicate in HeLa cells, indicating that the virB operon plays a critical role in intracellular multiplication [Ref6471:Höppner et al., 2005].
Polar mutations in the virB1 to virB2 intergenic region or in virB2 reduced the detection of VirB5 to a greater extent than they did that of VirB12. A virB1 mutation also eliminates the transcription of virB12 in B suis [Ref6471:Höppner et al., 2005].
An infection assay with signature-tagged Brucella abortus mutants demonstrated that mutagenesis of the virB1 gene causes attenuation of virulence [Ref6471:Höppner et al., 2005]. |
16272371
|
|
|
hemH from Brucella suis 1330 |
Brucella suis 1330 |
1164513
|
|
23499843
|
BRA0076 |
|
NP_699283.1 |
ferrochelatase |
Virulence factor |
FUNCTION: Catalyzes the ferrous insertion into protoporphyrin IX(Swiss-Prot: P0A3D7).
CATALYTIC ACTIVITY: Protoporphyrin + Fe(2+) = protoheme + 2 H(+)(Swiss-Prot: P0A3D7).
PATHWAY: Protoheme biosynthesis; last step(Swiss-Prot: P0A3D7).
SUBCELLULAR LOCATION: Cytoplasm (By similarity)(Swiss-Prot: P0A3D7).
SIMILARITY: Belongs to the ferrochelatase family(Swiss-Prot: P0A3D7).
MUTATION: A hemH knockout B. abortus mutant displayed auxotrophy for hemin, defective intracellular survival inside J774 and HeLa cells, and lack of virulence in BALBc mice. This phenotype was overcome by complementing the mutant strain with a plasmid harboring wild-type hemH. These data demonstrate that B abortus synthesizes its own heme and also has the ability to use an external source of heme [Ref6472:Almirón et al., 2001]. |
11553564
|
|
|
omp10 from Brucella suis 1330 |
Brucella suis 1330 |
1164514
|
|
23499844
|
BRA0077 |
|
NP_699284.1 |
lipoprotein Omp10 |
Virulence factor |
SUBCELLULAR LOCATION: Outer membrane; lipid-anchor(Swiss-Prot: P0A3N9).
MISCELLANEOUS: Elicits an immune response in B.melitensis-infected sheep but not in B.abortus-infected cattle(Swiss-Prot: P0A3N9).
SIMILARITY: Belongs to the rhizobiaceae omp10 lipoprotein family(Swiss-Prot: P0A3N9).
MUTATION: Omp10 is an immunoreactive outer membrane lipoprotein. The omp10 mutant was dramatically attenuated for survival in mice and was defective for growth in minimal medium but was not impaired in intracellular growth in vitro, nor does it display clear modification of the outer membrane properties [Ref6473:Tibor et al., 2002]. |
12228280
|
|
|
gnd from Brucella suis 1330 |
Brucella suis 1330 |
1164548
|
|
23499876
|
BRA0111 |
|
NP_699316.1 |
6-phosphogluconate dehydrogenase |
Virulence factor |
MUTATION: gnd is involved in pentose phosphate pathway. It is essential for intracellular growth inside HeLa cells as shown by its Brucella suis miniTn5Km2 transposon mutation analysis. The mutant is attenuated in the mouse model [Ref6469:Kim et al., 2003]. |
12761078
|
|
|
vjbR from Brucella suis 1330 |
Brucella suis 1330 |
1164556
|
|
23499883
|
BRA0119 |
|
NP_699323.1 |
transcriptional regulator, LuxR family |
Virulence factor |
FUNCTIONAL GROUP: Regulation [Ref6462:Delrue et al., 2004].
FUNCTION: Transcriptional regulator [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
gtrB from Brucella suis 1330 |
Brucella suis 1330 |
1164572
|
|
23499898
|
BRA0135 |
|
NP_699338.1 |
glycosyl transferase, group 2 family protein |
Virulence factor |
FUNCTIONAL GROUP: a.a. metabolism, Unkown [Ref6462:Delrue et al., 2004].
FUNCTION: glycosyl transerase [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Macrophages [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
deoR from Brucella suis 1330 |
Brucella suis 1330 |
1164583
|
|
23499909
|
BRA0146 |
|
NP_699349.1 |
transcriptional regulator, DeoR family |
Virulence factor |
FUNCTIONAL GROUP: Regulation [Ref6462:Delrue et al., 2004].
FUNCTION: Transcriptional regulator [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Macrophages [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
flgI from Brucella suis 1330 |
Brucella suis 1330 |
1164593
|
|
161486704
|
BRA0156 |
|
NP_699358.2 |
flagellar basal body P-ring protein |
Virulence factor |
FUNCTIONAL GROUP: "Classical virulence factors", Secretion of transport system, Flagella [Ref6462:Delrue et al., 2004].
FUNCTION: P-ring [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Mice, but not in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
gntR from Brucella suis 1330 |
Brucella suis 1330 |
1164614
|
|
23499939
|
BRA0177 |
|
NP_699379.1 |
transcriptional regulator, GntR family |
Virulence factor |
FUNCTIONAL GROUP: Regulation [Ref6462:Delrue et al., 2004].
FUNCTION: Transcriptional regulator [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
gluP from Brucella suis 1330 |
Brucella suis 1330 |
1164627
|
|
0
|
BRA0190 |
|
- |
- |
Virulence factor |
FUNCTION: Intake of glucose and galactose (Potential)(Swiss-Prot: Q8YB48).
SUBCELLULAR LOCATION: Inner membrane; multi-pass membrane protein (Probable)(Swiss-Prot: Q8YB48).
SIMILARITY: Belongs to the major facilitator superfamily. FHS transporter (TC 2.A.1.7) family(Swiss-Prot: Q8YB48).
MUTATION: B suis and maybe B canis seem to have two glucosegalactose transporters: gluP and gguAB. B abortus may express only gluP, which may explain why gluP mutants fail to survive long periods in the mouse [Ref6474:Essenberg et al., 2002]. |
12414147
|
|
|
caiB from Brucella suis 1330 |
Brucella suis 1330 |
1164661
|
|
23499983
|
BRA0224 |
|
NP_699423.1 |
CAIB/BAIF family protein |
Virulence factor |
FUNCTIONAL GROUP: Oxidoreduction [Ref6462:Delrue et al., 2004].
FUNCTION: CAIB/BAIF family [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Macrophages [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
norE from Brucella suis 1330 |
Brucella suis 1330 |
1164683
|
|
23500003
|
BRA0246 |
|
NP_699443.1 |
cytochrome c oxidase, subunit III |
Virulence factor |
FUNCTIONAL GROUP: Oxidoreduction [Ref6462:Delrue et al., 2004].
FUNCTION: Nitric oxide reduction [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Mice, but not in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
norD |
Brucella |
1164688
|
|
23500008
|
BRA0251 |
|
NP_699448.1 |
norD protein |
Virulence factor |
MUTATION: A mutant of Brucella suis bearing a Tn5 insertion in norD , the last gene of the operon norEFCBQD, encoding nitric oxide reductase, was unable to survive under anaerobic denitrifying conditions (more-than-5log reduction in viable counts). As a consequence of the norD mutation , NO might not be further reduced to N2O by the NO reductase and it could become toxic for the bacteria. The infection of resting macrophages showed that the norD mutant and the wild-type strain displayed similar rates of multiplication. On the contrary, activation of J774A.1 cells by LPS and IFN was accompanied by a more-thantenfold attenuation of the norD mutant at 48 h p. i. [Ref6475:Loisel-Meyer et al., 2006]. |
16495577
|
|
|
narG from Brucella suis 1330 |
Brucella suis 1330 |
1164736
|
|
23500054
|
BRA0299 |
|
NP_699494.1 |
respiratory nitrate reductase, alpha subunit |
Virulence factor |
MUTATION: The narG gene encodes for an essential component of the dissimilatory nitrate reductase complex. This complex is encoded by the narGHIJ locus, which is present in the B suis genome together with the gene of the nitrite extrusion protein, narK. The narG mutant was unable to produce nitrite from nitrate [Ref412:Kohler et al., 2002]. A study with miniTn5 mutants of B. suis constitutively expressing gfp indicates that B. suis xx gene is required for intracellular multiplication in human macrophage THP-1 cells [Ref412:Kohler et al., 2002]. |
12438693
|
|
|
nrdH from Brucella suis 1330 |
Brucella suis 1330 |
1164751
|
|
23500069
|
BRA0314 |
|
NP_699509.1 |
glutaredoxin-like protein nrdH |
Virulence factor |
FUNCTIONAL GROUP: DNA/RNA metabolism, Synthesis [Ref6462:Delrue et al., 2004].
FUNCTION: Ribonucleotide recuctase [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in HeLa, but not in Macrophages, mice [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
wbpW from Brucella suis 1330 |
Brucella suis 1330 |
1164785
|
|
23500100
|
BRA0347 |
|
NP_699540.1 |
mannose-1-phosphate guanylyltransferase/mannose-6-phosphate isomerase |
Virulence factor |
FUNCTIONAL GROUP: "Classical virulence factors", Envelope molecules, Lipopolysaccharide [Ref6462:Delrue et al., 2004].
FUNCTION: O-chain biosynthesis [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Macrophages [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
manB from Brucella suis 1330 |
Brucella suis 1330 |
1164786
|
|
23500101
|
BRA0348 |
|
NP_699541.1 |
phosphoglucomutase, putative |
Virulence factor |
FUNCTIONAL GROUP: "Classical virulence factors", Envelope molecules, Lipopolysaccharide [Ref6462:Delrue et al., 2004].
FUNCTION: O-chain biosynthesis [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
oxyR |
Brucella suis 1330 |
1164792
|
|
23500107
|
BRA0354 |
AE014292 |
NP_699547 |
transcriptional regulator OxyR |
Virulence factor |
MUTATION: The transcription product of Brucella abortus oxyR binds to the B abortus catalase promoter region. A gene replacementdeletion Brucella oxyR mutant exhibits increased sensitivity to prolonged exposure to H2O2 and is unable to adapt to H2O2 in the environment [Ref6476:Kim and Mayfield, 2000]. |
10986275
|
|
|
xfp from Brucella suis 1330 |
Brucella suis 1330 |
1164823
|
|
23500138
|
BRA0385 |
|
NP_699578.1 |
putative phosphoketolase |
Virulence factor |
FUNCTIONAL GROUP: a.a. metabolism, Degradation [Ref6462:Delrue et al., 2004].
FUNCTION: Lys. degradation [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
glpK from Brucella suis 1330 |
Brucella suis 1330 |
1164881
|
|
23500192
|
BRA0443 |
|
NP_699632.1 |
glycerol kinase |
Virulence factor |
FUNCTION: Key enzyme in the regulation of glycerol uptake and metabolism(Swiss-Prot: Q8FWK8).
CATALYTIC ACTIVITY: ATP + glycerol = ADP + sn-glycerol 3-phosphate(Swiss-Prot: Q8FWK8).
PATHWAY: Glycerol utilization; first (rate-limiting) step(Swiss-Prot: Q8FWK8).
SIMILARITY: Belongs to the FGGY kinase family(Swiss-Prot: Q8FWK8).
MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
ssuB from Brucella suis 1330 |
Brucella suis 1330 |
1164905
|
|
23500215
|
BRA0467 |
|
NP_699655.1 |
taurine ABC transporter, permease protein, putative |
Virulence factor |
FUNCTIONAL GROUP: "Classical virulence factors", Secretion of transport system, Transpter [Ref6462:Delrue et al., 2004].
FUNCTION: Permease [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Differential fluorescence induction [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
cydD from Brucella suis 1330 |
Brucella suis 1330 |
1164946
|
|
23500255
|
BRA0508 |
|
NP_699695.1 |
ABC transporter, ATP-binding protein CydD |
Virulence factor |
MUTATION: The cydB and cydD mutants are also defective for the intracellular growth of B abortus and B suis, suggesting that functional cytochrome bd oxidase is required for growth in an intracellular environment [Ref6469:Kim et al., 2003]. |
12761078
|
|
|
cydC from Brucella suis 1330 |
Brucella suis 1330 |
1164947
|
|
23500256
|
BRA0509 |
|
NP_699696.1 |
ABC transporter, ATP-binding/permease protein |
Virulence factor |
FUNCTIONAL GROUP: Oxidoreduction [Ref6462:Delrue et al., 2004].
FUNCTION: Cytochrome oxidase [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
cydB from Brucella suis 1330 |
Brucella suis 1330 |
1164949
|
|
23500258
|
BRA0511 |
|
NP_699698.1 |
cytochrome d ubiquinol oxidase, subunit II |
Virulence factor |
MUTATION: cydB is a gene that is part of the cydAB operon encoding cytochrome bd oxidase , which catalyzes an alternate terminal electron transport step in bacterial respiration. Transposon (Tn5) mutagenesis of B abortus cydB was severely attenuated for intracellular survival. Unlike the virulent strain 2308, the Brucella cydB::Tn5 mutant was severely compromised for survival in the spleens of inoculated mice [Ref6477:Endley et al., 2001]. The cydB and cydD mutants are also defective for the intracellular growth of B abortus and B suis, suggesting that functional cytochrome bd oxidase is required for growth in an intracellular environment [Ref6477:Endley et al., 2001]. |
11274104
|
|
|
rbsC from Brucella suis 1330 |
Brucella suis 1330 |
1165007
|
|
23500312
|
BRA0568 |
|
NP_699752.1 |
ABC transporter, permease protein |
Virulence factor |
FUNCTIONAL GROUP: "Classical virulence factors", Secretion of transport system, Transpter [Ref6462:Delrue et al., 2004].
FUNCTION: ABC transporter [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
pcs |
Brucella suis 1330 |
1165011
|
|
23500316
|
BRA0572 |
AE014292 |
NP_699756 |
phosphatidylcholine synthase |
Virulence factor |
MUTATION: The role of Phosphatidylcholine (PC) in Brucella abortus was examined by generating mutants in pcs (BApcs) and pmtA (BApmtA), which encode key enzymes of the two bacterial PC biosynthetic routes, the choline and methyl-transferase pathways. In rich medium, BApcs and the double mutant BApcspmtA but not BApmtA displayed reduced growth, increased phosphatidylethanolamine and no PC, showing that Pcs is essential for PC synthesis under these conditions. In minimal medium, the parental strain, BApcs and BApmtA showed reduced but significant amounts of PC suggesting that PmtA may also be functional Probing with phage Tb, antibiotics, polycations and serum demonstrated that all mutants had altered envelopes. In macrophages, BApcs and BApcspmtA showed reduced ability to evade fusion with lysosomes and establish a replication niche. In mice, BApcs showed attenuation only at early times after infection, BApmtA at later stages and BApcspmtA throughout. The results suggest that Pcs and PmtA have complementary roles in vivo related to nutrient availability and that PC and the membrane properties that depend on this typical eukaryotic phospholipid are essential for Brucella virulence [Ref6478:Conde-Alvarez et al., 2006]. |
16882035
|
|
|
aidB from Brucella suis 1330 |
Brucella suis 1330 |
1165038
|
|
23500342
|
BRA0598 |
|
NP_699782.1 |
acyl-CoA dehydrogenase family protein |
Virulence factor |
FUNCTIONAL GROUP: DNA/RNA metabolism, Repair [Ref6462:Delrue et al., 2004].
FUNCTION: Protection against alkylation damage to DNA [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Macrophages [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
pyrB from Brucella suis 1330 |
Brucella suis 1330 |
1165039
|
|
23500343
|
BRA0599 |
|
NP_699783.1 |
aspartate carbamoyltransferase catalytic subunit |
Virulence factor |
CATALYTIC ACTIVITY: Carbamoyl phosphate + L-aspartate = phosphate + N-carbamoyl-L-aspartate(Swiss-Prot: P65612).
PATHWAY: Nucleotide biosynthesis; UMP biosynthesis; UMP from HCO(3)(-): step 2(Swiss-Prot: P65612).
PATHWAY: Context: Pyrimidine biosynthesis(Swiss-Prot: P65612).
SIMILARITY: Belongs to the ATCase/OTCase family(Swiss-Prot: P65612).
MUTATION: B. abortus pyrB (pyrimidines) gene is essential for intracellular growth in HeLa cells as shown from transposon mutagenesis study [Ref6469:Kim et al., 2003]. |
12761078
|
|
|
divK from Brucella suis 1330 |
Brucella suis 1330 |
1165052
|
|
23500356
|
BRA0612 |
|
NP_699796.1 |
polar differentiation response regulator |
Virulence factor |
FUNCTIONAL GROUP: Regulation [Ref6462:Delrue et al., 2004].
FUNCTION: Response regulator [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Mice [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
ugpB from Brucella suis 1330 |
Brucella suis 1330 |
1165097
|
|
23500399
|
BRA0655 |
|
NP_699839.1 |
glycerol-3-phosphate ABC transporter, periplasmic glycerol-3-phosphate-binding protein |
Virulence factor |
MUTATION: B suis ugpB mutant does not contain SP41 protein. Mutants lacking SP41 production are less invasive, but proliferate in HeLa cells. An isogenic DeltaugpB mutant showed a significant inhibitory effect on Brucella adherence and invasion of human cultured epithelial cells and this effect could be reversed by restoration of the ugpB on a plasmid. [Ref6479:Castañeda-Roldán et al., 2006]. |
16817909
|
|
|
ugpA from Brucella suis 1330 |
Brucella suis 1330 |
1165098
|
|
23500400
|
BRA0656 |
|
NP_699840.1 |
glycerol-3-phosphate ABC transporter, permease protein |
Virulence factor |
MUTATION: UgpA is one of the attenuated Signature-Tagged Mutagenesis mutants of Brucella melitensis identified during the acute phase of infection in mice [Ref6480:Lestrate et al., 2003]. |
14638795
|
|
|
ugpA from Brucella suis 1330 |
Brucella suis 1330 |
1165134
|
|
23500433
|
BRA0692 |
|
NP_699873.1 |
sugar ABC transporter, permease protein, putative |
Virulence factor |
MUTATION: UgpA is one of the attenuated Signature-Tagged Mutagenesis mutants of Brucella melitensis identified during the acute phase of infection in mice [Ref6480:Lestrate et al., 2003]. |
14638795
|
|
|
fbpA from Brucella suis 1330 |
Brucella suis 1330 |
1165142
|
|
23500440
|
BRA0700 |
|
NP_699880.1 |
iron compound ABC transporter, periplasmic iron compound-binding protein, putative |
Virulence factor |
FUNCTIONAL GROUP: Metal acquisition [Ref6462:Delrue et al., 2004].
FUNCTION: Fe3+ binding [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Differential fluorescence induction [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
sodC from Brucella suis 1330 |
Brucella suis 1330 |
1165145
|
|
23500443
|
BRA0703 |
|
NP_699883.1 |
superoxide dismutase, Cu-Zn |
Virulence factor |
FUNCTION: Destroys radicals which are normally produced within the cells and which are toxic to biological systems (By similarity)(Swiss-Prot: P66827).
CATALYTIC ACTIVITY: 2 superoxide + 2 H(+) = O(2) + H(2)O(2)(Swiss-Prot: P66827).
COFACTOR: Binds 1 copper ion per subunit (By similarity)(Swiss-Prot: P66827).
COFACTOR: Binds 1 zinc ion per subunit (By similarity)(Swiss-Prot: P66827).
SUBUNIT: Homodimer (By similarity)(Swiss-Prot: P66827).
SUBCELLULAR LOCATION: Periplasmic (By similarity)(Swiss-Prot: P66827).
SIMILARITY: Belongs to the Cu-Zn superoxide dismutase family(Swiss-Prot: P66827).
IMMUNOGENICITY: Induces antigen-specific Th1 immune response, as indicated by the specific induction of serum IgG2a, but not IgG1, antibodies and by the secretion of IFN-γ, but not IL-4, by the Cu/Zn SOD-stimulated splenocytes. Has been used for vaccine development [Ref6481:He et al., 2002][Ref6481:He et al., 2002][Ref6481:He et al., 2002].
MUTATION: An isogenic sodC mutant constructed from B abortus 2308 by gene replacement exhibited much greater susceptibility to killing by exogenous O(2)(-) than the parental 2308 strain, supporting a role for SodC in protecting this bacterium from O(2)(-) stress. The B abortus sodC mutant was much more sensitive to killing by cultured resident peritoneal macrophages from C57BL6J mice than 2308, and its attenuation in cultured murine macrophages was enhanced when these phagocytes were treated with gamma interferon. The attenuation of the B abortus sodC mutant in both resting and IFN-gamma -activated macrophages was alleviated in the presence of the NADPH oxidase inhibitor apocynin. Consistently, the B abortus sodC mutant also displayed significant attenuation in infected C57BL6J mice compared to the parental strain. These findings suggest that SodC protects B abortus 2308 from the respiratory burst of host macrophages [Ref6481:He et al., 2002]. |
11953393
|
|
|
RpiR from Brucella suis 1330 |
Brucella suis 1330 |
1165154
|
|
23500452
|
BRA0712 |
|
NP_699892.1 |
SIS domain protein |
Virulence factor |
FUNCTIONAL GROUP: Regulation [Ref6462:Delrue et al., 2004].
FUNCTION: Transcriptional regulator [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Mice, but not in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
gcvP from Brucella suis 1330 |
Brucella suis 1330 |
1165167
|
|
23500462
|
BRA0725 |
|
NP_699902.1 |
glycine dehydrogenase |
Virulence factor |
FUNCTION: The glycine cleavage system catalyzes the degradation of glycine. The P protein binds the alpha-amino group of glycine through its pyridoxal phosphate cofactor; CO(2) is released and the remaining methylamine moiety is then transferred to the lipoamide cofactor of the H protein (By similarity)(Swiss-Prot: Q8FVU9).
CATALYTIC ACTIVITY: Glycine + H-protein-lipoyllysine = H-protein-S-aminomethyldihydrolipoyllysine + CO(2)(Swiss-Prot: Q8FVU9).
COFACTOR: Pyridoxal phosphate (By similarity)(Swiss-Prot: Q8FVU9).
SUBUNIT: The glycine cleavage system is composed of four proteins: P, T, L and H (By similarity)(Swiss-Prot: Q8FVU9).
SIMILARITY: Belongs to the gcvP family(Swiss-Prot: Q8FVU9).
MUTATION: gcvP encodes for glycine dehydrogenase and is required for persistent infection in mouse model [Ref6482:Ficht, 2003]. |
12523983
|
|
|
gcvT from Brucella suis 1330 |
Brucella suis 1330 |
1165169
|
|
23500464
|
BRA0727 |
|
NP_699904.1 |
glycine cleavage system T protein |
Virulence factor |
MUTATION: A study with miniTn5 mutants of B. suis constitutively expressing gfp indicates that B. suis gcvT gene is required for intracellular multiplication in human macrophage THP-1 cells [Ref412:Kohler et al., 2002]. |
12438693
|
|
|
xseA from Brucella suis 1330 |
Brucella suis 1330 |
1165206
|
|
23500501
|
BRA0764 |
|
NP_699941.1 |
exodeoxyribonuclease VII large subunit |
Virulence factor |
FUNCTION: Bidirectionally degrades single-stranded DNA into large acid-insoluble oligonucleotides, which are then degraded further into small acid-soluble oligonucleotides (By similarity)(Swiss-Prot: Q8FVR1).
CATALYTIC ACTIVITY: Exonucleolytic cleavage in either 5'- to 3'- or 3'- to 5'-direction to yield nucleoside 5'-phosphates(Swiss-Prot: Q8FVR1).
SUBUNIT: Heterooligomer composed of large and small subunits (By similarity)(Swiss-Prot: Q8FVR1).
SUBCELLULAR LOCATION: Cytoplasm (By similarity)(Swiss-Prot: Q8FVR1).
SIMILARITY: Belongs to the xseA family(Swiss-Prot: Q8FVR1).
MUTATION: xseA codes for an exodeoxyribonuclease. B. melitensis xseA mutant via signature-tagged mutagenesis is attenuated in vivo in mice [Ref6480:Lestrate et al., 2003]. |
14638795
|
|
|
zwf from Brucella suis 1330 |
Brucella suis 1330 |
1165220
|
|
23500514
|
BRA0778 |
|
NP_699954.1 |
glucose-6-phosphate 1-dehydrogenase |
Virulence factor |
MUTATION: Brucella abortus zwf mutant via mini-Tn5Km2 transposon mutagenesis has intracellular growth defect inside HeLa cells and macrophages [Ref6469:Kim et al., 2003]. |
12761078
|
|
|
nikA from Brucella suis 1330 |
Brucella suis 1330 |
1165246
|
|
23500537
|
BRA0804 |
|
NP_699977.1 |
nickel ABC transporter, nickel-binding protein, putative |
Virulence factor |
FUNCTIONAL GROUP: Metal acquisition [Ref6462:Delrue et al., 2004].
FUNCTION: Ni2+ uptake [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Differential fluorescence induction, but not in Macrophages, Mice [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
galcD from Brucella suis 1330 |
Brucella suis 1330 |
1165248
|
|
23500539
|
BRA0806 |
|
NP_699979.1 |
hydrolase, UxaA family |
Virulence factor |
FUNCTIONAL GROUP: a.a. metabolism, Unkown [Ref6462:Delrue et al., 2004].
FUNCTION: D-galactarate dehydratase [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
eryB from Brucella suis 1330 |
Brucella suis 1330 |
1165308
|
|
23500593
|
BRA0865 |
|
NP_700033.1 |
glycerol-3-phosphate dehydrogenase |
Virulence factor |
MUTATION: EryB is an erythritol phosphate dehydrogenase. The vaccine strain B abortus B19 is the only known B abortus isolate whose growth is inhibited by erythritol. The B abortus B19 strain is an eryCD double mutant. The defect in B19 was complemented in trans by plasmids containing the complete ery region and by plasmids with Tn1725 insertions in eryA, eryB and eryD. Plasmids with Tn1725 insertions in eryC were the only ones that failed to complement the Ery phenotype of B19 [Ref6483:Sangari et al., 2000].
The B. suis eryB mutant by Tn5 transposon mutagenesis was attenuated in the human macrophage -like THP-1 cells. This mutant is sensitive to erythritol and mimics the erythritol sensitive response of the B19 strain [Ref6483:Sangari et al., 2000]. |
10708387
|
|
|
eryC from Brucella suis 1330 |
Brucella suis 1330 |
1165309
|
|
23500594
|
BRA0866 |
|
NP_700034.1 |
D-erythrulose-1-phosphate dehydrogenase |
Virulence factor |
MUTATION: The eryC gene encodes for enzyme Derythrulose-1-phosphate dehydrogenase. The vaccine strain B abortus B19 is the only known B abortus isolate whose growth is inhibited by erythritol. The B abortus B19 strain is an eryCD double mutant. The defect in B19 was complemented in trans by plasmids containing the complete ery region and by plasmids with Tn1725 insertions in eryA, eryB and eryD. Plasmids with Tn1725 insertions in eryC were the only ones that failed to complement the Ery phenotype of B19 [Ref6483:Sangari et al., 2000].
Allelic exchange mutants in eryC of Brucella suis were erythritol sensitive in vitro with a MIC of 1 to 5 mM of erythritol. Their multiplication in macrophage-like cells was 50 to 90- fold reduced , but complementation of the mutant restored wild-type levels of intracellular multiplication and the capacity to use erythritol as a sole carbon source. In vivo, the eryC mutant colonized the spleens of infected BALBc mice to a significantly lower extent than the wild type and the complemented strain. Interestingly, eryC mutants that were in addition spontaneously erythritol tolerant nevertheless exhibited wild-type-like intramacrophagic and intramurine replication. In conclusion, erythritol was not an essential carbon source for the pathogen in the macrophage host cell but that the inactivation of the eryC gene significantly reduced the intramacrophagic and intramurine fitness of B suis [Ref6483:Sangari et al., 2000]. |
10708387
|
|
|
fdhA from Brucella suis 1330 |
Brucella suis 1330 |
1165363
|
|
23500646
|
BRA0919 |
|
NP_700086.1 |
oxidoreductase, molybdopterin-binding, putative |
Virulence factor |
FUNCTIONAL GROUP: Oxidoreduction [Ref6462:Delrue et al., 2004].
FUNCTION: Formate dehydrogenase [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Mice [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
araG from Brucella suis 1330 |
Brucella suis 1330 |
1165380
|
|
23500663
|
BRA0936 |
|
NP_700103.1 |
sugar ABC transporter, ATP-binding protein |
Virulence factor |
FUNCTIONAL GROUP: a.a. metabolism, Transport [Ref6462:Delrue et al., 2004].
FUNCTION: L-arabinose transport [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Differential fluorescence induction, but not in Macrophages [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
dacF from Brucella suis 1330 |
Brucella suis 1330 |
1165391
|
|
23500673
|
BRA0947 |
|
NP_700113.1 |
D-aminopeptidase |
Virulence factor |
FUNCTIONAL GROUP: "Classical virulence factors", Envelope molecules, peptidoglycan [Ref6462:Delrue et al., 2004].
FUNCTION: Peptidoglycan synthesis [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
cobW from Brucella suis 1330 |
Brucella suis 1330 |
1165431
|
|
23500711
|
BRA0987 |
|
NP_700151.1 |
cobalamin synthesis protein/P47K family protein |
Virulence factor |
MUTATION: A study with miniTn5 mutants of B. suis constitutively expressing gfp indicates that B. suis cobW gene is required for intracellular multiplication in human macrophage THP-1 cells [Ref412:Kohler et al., 2002]. |
12438693
|
|
|
dppA from Brucella suis 1330 |
Brucella suis 1330 |
1165456
|
|
23500735
|
BRA1012 |
|
NP_700175.1 |
ABC transporter, periplasmic substrate-binding protein |
Virulence factor |
FUNCTIONAL GROUP: a.a. metabolism, Transport [Ref6462:Delrue et al., 2004].
FUNCTION: Dipeptide uptake [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
znuA from Brucella suis 1330 |
Brucella suis 1330 |
1165575
|
|
23500837
|
BRA1122 |
|
NP_700277.1 |
zinc ABC transporter, periplasmic zinc-binding protein |
Virulence factor |
MUTATION: Brucella abortus znuA mutant via mini-Tn5Km2 transposon mutagenesis has intracellular growth defect inside HeLa cells [Ref6469:Kim et al., 2003]. High-affinity zinc uptake system protein mutant (znuA mutant) showed reduced growth in zinc chelated medium, and failed to replicate in HeLa cells and mouse bone marrow-derived macrophages. Transformation of znuA mutant with a shuttle vector pBBR1MCS-4 containing znuA gene restored the growth in zinc chelated medium and intracellular replication in HeLa cells and macrophages to a level comparable to that of wild-type strain. Bacterial internalization into HeLa cells and macrophages and co-localization with either late endosomes or lysosomes of znuA mutant were not different from those of wild-type strain. These results suggest that znuA does not contribute to intracellular trafficking of B abortus, but contributes to utilization of zinc required for intracellular growth [Ref6469:Kim et al., 2003]. |
12761078
|
|
|
znuC from Brucella suis 1330 |
Brucella suis 1330 |
1165576
|
|
23500838
|
BRA1123 |
|
NP_700278.1 |
zinc ABC transporter, ATP-binding protein |
Virulence factor |
FUNCTIONAL GROUP: Metal acquisition [Ref6462:Delrue et al., 2004].
FUNCTION: Zn2+ uptake [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
flgE from Brucella suis 1330 |
Brucella suis 1330 |
1165592
|
|
23500854
|
BRA1139 |
|
NP_700294.1 |
flagellar hook protein FlgE |
Virulence factor |
FUNCTIONAL GROUP: "Classical virulence factors", Secretion of transport system, Flagella [Ref6462:Delrue et al., 2004].
FUNCTION: Hook [Ref6462:Delrue et al., 2004].
SIMILARITY: Belongs to the flagella basal body rod proteins family(Swiss-Prot: Q8FUS9).
MUTATION: Attenuated in Mice, but not in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
motB from Brucella suis 1330 |
Brucella from Brucella suis 1330 |
1165597
|
|
23500858
|
BRA1144 |
|
NP_700298.1 |
flagellar motor protein MotB |
Virulence factor |
FUNCTIONAL GROUP: "Classical virulence factors", Secretion of transport system, Flagella [Ref6462:Delrue et al., 2004].
FUNCTION: Flagellar motor [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Mice, but not in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
fliF from Brucella suis 1330 |
Brucella suis 1330 |
1165599
|
|
23500860
|
BRA1146 |
|
NP_700300.1 |
flagellar MS-ring protein |
Virulence factor |
FUNCTION: The M ring may be actively involved in energy transduction (By similarity)(Swiss-Prot: Q8FUS3).
SUBUNIT: The basal body constitutes a major portion of the flagellar organelle and consists of five rings (E,L,P,S, and M) mounted on a central rod. The M ring is integral to the inner membrane of the cell and may be connected to the flagellar rod via the S ring. The S (supramembrane ring) lies just distal to the M ring. The L and P rings lie in the outer membrane and the periplasmic space, respectively (By similarity)(Swiss-Prot: Q8FUS3).
SUBCELLULAR LOCATION: Inner membrane; multi-pass membrane protein (By similarity)(Swiss-Prot: Q8FUS3).
SIMILARITY: Belongs to the fliF family(Swiss-Prot: Q8FUS3).
MUTATION: fliF is a gene potentially coding for the MS ring, a basal component of the flagellar system. Its mutant through signature- tagged mutagenesis is attenuated in vivo. It implicate a role for flagella in virulenc [Ref6480:Lestrate et al., 2003]. |
14638795
|
|
|
rpsA from Brucella suis 1330 |
Brucella suis 1330 |
1165684
|
|
23500942
|
BR0027 |
|
NP_697069.1 |
30S ribosomal protein S1 |
Virulence factor |
MUTATION: rpsA is a B. suis gene identified by signature-tagged mutagenesis [Ref6484:Foulongne et al., 2000]. |
10678941
|
|
|
pheA from Brucella suis 1330 |
Brucella suis 1330 |
1165694
|
|
23500952
|
BR0037 |
|
NP_697079.1 |
prephenate dehydratase |
Virulence factor |
MUTATION: The product of pheA gene is specifically dedicated to the biosynthesis of phenylalanine. The B. abortus pheA mutant with mini-Tn5 disruption displays nutritional defects in vitro. Experimental findings with the B abortus ilvD, trpB, and pheA mutants suggest that tryptophan and phenylalanine are available to the brucellae in their intracellular niche but that other amino acids (eg, leucine, isoleucine, or valine) are not. The pheA::miniTn5 mutant displayed attenuation in macrophages but not in mice [Ref6485:Alcantara et al., 2004]. |
15271960
|
|
|
pgm from Brucella suis 1330 |
Brucella suis 1330 |
1165715
|
|
23500973
|
BR0058 |
|
NP_697100.1 |
phosphoglucomutase |
Virulence factor |
MUTATION: Brucella pgm encodes the phosphoglucomutase. The B. abortus pgm mutant (B2211) lacks the O antigen. However, the core region of the mutant LPS migrated in Tricine-PAGE electrophoresis in a position that was indistinguishable from that of the wild type core. Although the exponential intracellular replication of the pgm mutant was delayed by approximately 20 h with respect to that of the wild type, the high number of recoverable bacteria at 48 h postinfection indicates that mutant strain B2211 replicates inside HeLa host cells [Ref6486:Ugalde et al., 2000].
B abortus phosphoglucomutase (pgm) insertional mutants were attenuated in vivo but not in vitro [Ref6486:Ugalde et al., 2000]. |
10992476
|
|
|
ilvD from Brucella suis 1330 |
Brucella suis 1330 |
1165756
|
|
23501013
|
BR0099 |
|
NP_697140.1 |
dihydroxy-acid dehydratase |
Virulence factor |
CATALYTIC ACTIVITY: 2,3-dihydroxy-3-methylbutanoate = 3-methyl-2-oxobutanoate + H(2)O(Swiss-Prot: Q8G353).
COFACTOR: Binds 1 4Fe-4S cluster (Potential)(Swiss-Prot: Q8G353).
PATHWAY: Amino-acid biosynthesis; L-isoleucine biosynthesis; L-isoleucine from 2-oxobutanoate: step 3(Swiss-Prot: Q8G353).
PATHWAY: Amino-acid biosynthesis; L-valine biosynthesis; L-valine from pyruvate: step 3(Swiss-Prot: Q8G353).
SIMILARITY: Belongs to the ilvD/edd family(Swiss-Prot: Q8G353).
MUTATION: Of those B abortus mutants with mini-Tn5 insertions in genes predicted to be involved in amino acid biosynthesis and transport, only the ilvD mutant, displayed attenuation in both macrophages and mice. The othre two amino acid biosynthesis mutants [trpB::miniTn5 and pheA::miniTn5] displayed wild-type virulence in mice but attenuated inside macrophages. The studies with B abortus ilvD, trpB, and pheA mutants suggest that tryptophan and phenylalanine are available to the brucellae in their intracellular niche but that other amino acids (eg, leucine, isoleucine, or valine) are not [Ref6485:Alcantara et al., 2004]. |
15271960
|
|
|
ndvB from Brucella suis 1330 |
Brucella suis 1330 |
1165768
|
|
23501025
|
BR0111 |
|
NP_697152.1 |
cyclic beta 1-2 glucan synthetase |
Virulence factor |
FUNCTIONAL GROUP: a.a. metabolism, Unkown [Ref6462:Delrue et al., 2004].
FUNCTION: Synthesis of cyclic ( [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Mice, HeLa [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
glnD from Brucella suis 1330 |
Brucella suis 1330 |
1165801
|
|
23501056
|
BR0144 |
|
NP_697183.1 |
PII uridylyl-transferase |
Virulence factor |
FUNCTION: Modifies, by uridylylation or deuridylylation the PII (glnB) regulatory protein (By similarity)(Swiss-Prot: Q8G312).
CATALYTIC ACTIVITY: UTP + [protein-PII] = diphosphate + uridylyl-[protein-PII](Swiss-Prot: Q8G312).
SIMILARITY: Belongs to the glnD family(Swiss-Prot: Q8G312).
MUTATION: glnD encodes for a uridylyl transferase which is the primary sensor of nitrogen. The glnD mutant via signature-tagged transposon mutagenesis is attenuated in THP1 macrophages and HeLa cells. It supports the hypothesis that the concentration of glutamine in host cells is critical for the intracellular survival of Brucella [Ref6484:Foulongne et al., 2000]. |
10678941
|
|
|
cysI from Brucella suis 1330 |
Brucella suis 1330 |
1165838
|
|
23501092
|
BR0181 |
|
NP_697219.1 |
sulfite reductase (NADPH) hemoprotein beta-component |
Virulence factor |
FUNCTIONAL GROUP: Oxidoreduction [Ref6462:Delrue et al., 2004].
FUNCTION: Sulfite reductate [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Mice, Macrophages, but not in HeLa [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
metH from Brucella suis 1330 |
Brucella suis 1330 |
1165845
|
|
23501099
|
BR0188 |
|
NP_697226.1 |
B12-dependent methionine synthase |
Virulence factor |
FUNCTIONAL GROUP: a.a. metabolism, Synthesis [Ref6462:Delrue et al., 2004].
FUNCTION: Met. synthesis [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
malK from Brucella suis 1330 |
Brucella suis 1330 |
1165896
|
|
23501145
|
BR0238 |
|
NP_697272.1 |
sugar ABC transporter, ATP-binding protein |
Virulence factor |
FUNCTIONAL GROUP: a.a. metabolism, Transport [Ref6462:Delrue et al., 2004].
FUNCTION: Maltose transport [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Macrophages, but not in HeLa [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
hisD from Brucella suis 1330 |
Brucella suis 1330 |
1165911
|
|
23501159
|
BR0252 |
|
NP_697286.1 |
histidinol dehydrogenase |
Virulence factor |
FUNCTION: Catalyzes the sequential NAD-dependent oxidations of L-histidinol to L-histidinaldehyde and then to L-histidine (By similarity)(Swiss-Prot: Q8G2R2).
CATALYTIC ACTIVITY: L-histidinol + 2 NAD(+) = L-histidine + 2 NADH(Swiss-Prot: Q8G2R2).
COFACTOR: Binds 1 zinc ion per subunit (By similarity)(Swiss-Prot: Q8G2R2).
PATHWAY: Amino-acid biosynthesis; L-histidine biosynthesis; L-histidine from 5-phospho-alpha-D-ribose 1-diphosphate: step 9 [final step](Swiss-Prot: Q8G2R2).
SIMILARITY: Belongs to the histidinol dehydrogenase family(Swiss-Prot: Q8G2R2).
MUTATION: A study with miniTn5 mutants of B. suis constitutively expressing gfp indicates that B. suis hisD gene is required for intracellular multiplication in human macrophage THP-1 cells [Ref412:Kohler et al., 2002]. |
12438693
|
|
|
pgi from Brucella suis 1330 |
Brucella suis 1330 |
1165946
|
|
23501192
|
BR0285 |
|
NP_697319.1 |
glucose-6-phosphate isomerase |
Virulence factor |
CATALYTIC ACTIVITY: D-glucose 6-phosphate = D-fructose 6-phosphate(Swiss-Prot: Q8G2N3).
PATHWAY: Carbohydrate degradation; glycolysis; D-glyceraldehyde 3-phosphate and glycerone phosphate from D-glucose: step 2(Swiss-Prot: Q8G2N3).
SUBCELLULAR LOCATION: Cytoplasm (By similarity)(Swiss-Prot: Q8G2N3).
SIMILARITY: Belongs to the GPI family(Swiss-Prot: Q8G2N3).
MUTATION: B. suis pgi is a gene identified by signature-tagged mutagenesis. The mutant is attenuated inside THP1 macrophages. The mutation of the pgi gene could also affect the biosynthesis of the bacterial peptidoglycan [Ref6484:Foulongne et al., 2000]. |
10678941
|
|
|
pyrD from Brucella suis 1330 |
Brucella suis 1330 |
1165972
|
|
23501218
|
BR0311 |
|
NP_697345.1 |
dihydroorotate dehydrogenase 2 |
Virulence factor |
MUTATION: B. suis pyrD mutation study indicated that pyrimidine synthesis pathway contributes to intracellular growth [Ref6469:Kim et al., 2003]. |
12761078
|
|
|
vsrB from Brucella suis 1330 |
Brucella suis 1330 |
1165977
|
|
23501223
|
BR0316 |
|
NP_697350.1 |
sensor histidine kinase/response regulator |
Virulence factor |
FUNCTIONAL GROUP: Regulation [Ref6462:Delrue et al., 2004].
FUNCTION: Histidine kinase [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
bacA from Brucella suis 1330 |
Brucella suis 1330 |
1166033
|
|
23501276
|
BR0372 |
|
NP_697403.1 |
transport protein |
Virulence factor |
MUTATION: B abortus bacA mutant exhibited decreased survival in macrophages and greatly accelerated clearance from experimentally infected mice compared to the virulent parental strain [Ref6487:LeVier et al., 2000]. R meliloti bacA gene encodes a putative cytoplasmic membrane transport protein required for symbiosis [Ref6487:LeVier et al., 2000]. The BacA protein is essential for the long-term survival of Sinorhizobium meliloti and Brucella abortus within acidic compartments in plant and animal cells , respectively. Mutation study showed that B. abortus BacA affects the distribution of LPS fatty acids, including a very-long-chain fatty acid thought to be unique to the alpha-proteobacteria[Ref6487:LeVier et al., 2000]. |
10741969
|
|
|
purD from Brucella suis 1330 |
Brucella suis 1330 |
1166075
|
|
23501317
|
BR0414 |
|
NP_697444.1 |
phosphoribosylamine--glycine ligase |
Virulence factor |
CATALYTIC ACTIVITY: ATP + 5-phospho-D-ribosylamine + glycine = ADP + phosphate + N(1)-(5-phospho-D-ribosyl)glycinamide(Swiss-Prot: Q8G2B1).
PATHWAY: Nucleotide biosynthesis; IMP biosynthesis; N(1)-(5-phospho-D-ribosyl)glycinamide from 5-phospho-alpha-D-ribose 1-diphosphate: step 2(Swiss-Prot: Q8G2B1).
PATHWAY: Context: Purine biosynthesis(Swiss-Prot: Q8G2B1).
SIMILARITY: Belongs to the GARS family(Swiss-Prot: Q8G2B1).
SIMILARITY: Contains 1 ATP-grasp domain(Swiss-Prot: Q8G2B1).
MUTATION: Brucella abortus 2308 derivatives with mini-Tn5 insertions in purE, purL, and purD display significant attenuation in the BALBc mouse model. It confirms the importance of the purine biosynthesis pathways for the survival and replication of the brucellae in host macrophages [Ref6485:Alcantara et al., 2004].
Like the purE mutant, a purD::Tn10 mutant has reduced survival in murine macrophages and reduced virulence in mice [Ref6485:Alcantara et al., 2004]. |
15271960
|
|
|
aroC from Brucella suis 1330 |
Brucella suis 1330 |
1166089
|
|
23501329
|
BR0428 |
|
NP_697456.1 |
chorismate synthase |
Virulence factor |
CATALYTIC ACTIVITY: 5-O-(1-carboxyvinyl)-3-phosphoshikimate = chorismate + phosphate(Swiss-Prot: P63608).
COFACTOR: Reduced flavin (By similarity)(Swiss-Prot: P63608).
PATHWAY: Metabolic intermediate biosynthesis; chorismate biosynthesis; chorismate from D-erythrose 4-phosphate and PEP: step 7 [final step](Swiss-Prot: P63608).
PATHWAY: Context: Aromatic amino acids biosynthesis(Swiss-Prot: P63608).
SUBUNIT: Homotetramer (By similarity)(Swiss-Prot: P63608).
SIMILARITY: Belongs to the chorismate synthase family(Swiss-Prot: P63608).
MUTATION: The cloned aroC gene complements Escherichia coli and Salmonella enterica serovar Typhimurium aroC mutants. A B suis aroC mutant was found to be unable to grow in a defined medium without aromatic compounds. The mutant was highly attenuated in it issue culture (THP1 macrophages and HeLa cells) and murine virulence models [Ref6488:Foulongne et al., 2001]. |
11119550
|
|
|
exsA from Brucella suis 1330 |
Brucella suis 1330 |
1166103
|
|
23501343
|
BR0442 |
|
NP_697470.1 |
ABC transporter, ATP-binding/permease protein |
Virulence factor |
FUNCTIONAL GROUP: a.a. metabolism, Transport [Ref6462:Delrue et al., 2004].
FUNCTION: ABC transporter [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Mice [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
purF from Brucella suis 1330 |
Brucella suis 1330 |
1166107
|
|
23501347
|
BR0446 |
|
NP_697474.1 |
amidophosphoribosyltransferase |
Virulence factor |
MUTATION: A B. suis purF mutation experiment suggests that the purine biosynthesis pathway contributes to intracellular growth [Ref6469:Kim et al., 2003]. |
12761078
|
|
|
tldD from Brucella suis 1330 |
Brucella suis 1330 |
1166126
|
|
23501366
|
BR0465 |
|
NP_697493.1 |
tldD protein, putative |
Virulence factor |
FUNCTIONAL GROUP: DNA/RNA metabolism, Regulation [Ref6462:Delrue et al., 2004].
FUNCTION: Putative modulator of DNA gyrase [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Mice [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
thrC from Brucella suis 1330 |
Brucella suis 1330 |
1166145
|
|
23501385
|
BR0484 |
|
NP_697512.1 |
threonine synthase |
Virulence factor |
FUNCTIONAL GROUP: a.a. metabolism, Synthesis [Ref6462:Delrue et al., 2004].
FUNCTION: Thre. Synthesis [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Macrophages [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
dsbA from Brucella suis 1330 |
Brucella suis 1330 |
1166157
|
|
23501397
|
BR0496 |
|
NP_697524.1 |
twin-arginine translocation signal domain protein |
Virulence factor |
FUNCTIONAL GROUP: Oxidoreduction [Ref6462:Delrue et al., 2004].
FUNCTION: Disulfide bond formation protein [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
wbpL from Brucella suis 1330 |
Brucella suis 1330 |
1166172
|
|
23501411
|
BR0511 |
|
NP_697538.1 |
glycosyl transferase, group 4 family protein |
Virulence factor |
FUNCTIONAL GROUP: "Classical virulence factors", Envelope molecules, Lipopolysaccharide [Ref6462:Delrue et al., 2004].
FUNCTION: O-chain biosynthesis [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Mice, Macrophages [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
wbkB |
Brucella suis 1330 |
1166180
|
|
23501413
|
BR0518 |
AE014291 |
NP_697540 |
wbkB protein |
Virulence factor |
MUTATION: No function has been assigned to the B. melitensis 16M wbkB gene either by homology search or functionally, because deletion of wbkB did not interfere with the O-antigen structure [Ref6489:Godfroid et al., 2000]. |
11081580
|
|
|
rfbD from Brucella suis 1330 |
Brucella suis 1330 |
1166182
|
|
23501415
|
BR0520 |
|
NP_697542.1 |
O-antigen export system permease protein RfbD |
Virulence factor |
FUNCTIONAL GROUP: "Classical virulence factors", Envelope molecules, Lipopolysaccharide [Ref6462:Delrue et al., 2004].
FUNCTION: O-chain biosynthesis [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Mice, Macrophages [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
perA from Brucella suis 1330 |
Brucella suis 1330 |
1166183
|
|
23501416
|
BR0521 |
|
NP_697543.1 |
perosamine synthase, putative |
Virulence factor |
FUNCTIONAL GROUP: "Classical virulence factors", Envelope molecules, Lipopolysaccharide [Ref6462:Delrue et al., 2004].
FUNCTION: O-chain biosynthesis [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Macrophages [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
gmd from Brucella suis 1330 |
Brucella suis 1330 |
1166184
|
|
23501417
|
BR0522 |
|
NP_697544.1 |
GDP-mannose 4,6-dehydratase |
Virulence factor |
MUTATION: gmd may be involved in perosamine synthesis. It has been shown to be in LPS synthesis since its B. melitensis mutation induces rough phenotype [Ref6490:Moriyón et al., 2004]. |
15099501
|
|
|
wbkA from Brucella suis 1330 |
Brucella suis 1330 |
1166191
|
|
23501421
|
BR0529 |
|
NP_697548.1 |
mannosyltransferase, putative |
Virulence factor |
FUNCTIONAL GROUP: "Classical virulence factors", Envelope molecules, Lipopolysaccharide [Ref6462:Delrue et al., 2004].
FUNCTION: O-chain biosynthesis [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Mice [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
pmm from Brucella suis 1330 |
Brucella suis 1330 |
1166199
|
|
23501426
|
BR0537 |
|
NP_697553.1 |
phosphomannomutase, putative |
Virulence factor |
FUNCTIONAL GROUP: "Classical virulence factors", Envelope molecules, Lipopolysaccharide [Ref6462:Delrue et al., 2004].
FUNCTION: O-chain biosynthesis [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
wbpZ from Brucella suis 1330 |
Brucella suis 1330 |
1166202
|
|
23501429
|
BR0540 |
|
NP_697556.1 |
glycosyl transferase, group 1 family protein |
Virulence factor |
FUNCTIONAL GROUP: "Classical virulence factors", Envelope molecules, Lipopolysaccharide [Ref6462:Delrue et al., 2004].
FUNCTION: O-chain biosynthesis [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Mice, Macrophages [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
feuP from Brucella suis 1330 |
Brucella suis 1330 |
1166266
|
|
23501491
|
BR0604 |
|
NP_697618.1 |
DNA-binding response regulator |
Virulence factor |
FUNCTIONAL GROUP: Regulation [Ref6462:Delrue et al., 2004].
FUNCTION: Response regulator [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Mice, Macrophages [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
feuQ from Brucella suis 1330 |
Brucella suis 1330 |
1166267
|
|
23501492
|
BR0605 |
|
NP_697619.1 |
sensor histidine kinase |
Virulence factor |
FUNCTIONAL GROUP: Regulation [Ref6462:Delrue et al., 2004].
FUNCTION: Histidine kinase [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
htrA from Brucella suis 1330 |
Brucella suis 1330 |
1166273
|
|
23501498
|
BR0611 |
|
NP_697625.1 |
serine protease |
Virulence factor |
FUNCTIONAL GROUP: Stress proteins/Chaperones [Ref412:Kohler et al., 2002].
FUNCTION: Protease [Ref412:Kohler et al., 2002].
MUTATION: Attenuated in "Goat", Macrophages, but not in Mice [Ref412:Kohler et al., 2002]. |
12438693
|
|
|
lpsA from Brucella suis 1330 |
Brucella suis 1330 |
1166277
|
|
23501502
|
BR0615 |
|
NP_697629.1 |
hypothetical protein |
Virulence factor |
FUNCTIONAL GROUP: "Classical virulence factors", Envelope molecules, Lipopolysaccharide [Ref6462:Delrue et al., 2004].
FUNCTION: putative glycosyltranferase [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Macrophages [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
pepN from Brucella suis 1330 |
Brucella suis 1330 |
1166279
|
|
23501504
|
BR0617 |
|
NP_697631.1 |
aminopeptidase N |
Virulence factor |
MUTATION: A single mutation of PepN leads to a significant decrease in the growth rate, thus PepN seems to play a more prominent role than do the other proteases [Ref6491:Contreras-Rodriguez et al., 2003]. |
12933870
|
|
|
spotT from Brucella suis 1330 |
Brucella suis 1330 |
1166315
|
|
23501539
|
BR0652 |
|
NP_697666.1 |
RelA/SpoT family protein |
Virulence factor |
FUNCTIONAL GROUP: Regulation [Ref6462:Delrue et al., 2004].
FUNCTION: ppGpp synthetase [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
omp25 from Brucella suis 1330 |
Brucella suis 1330 |
1166364
|
|
23501588
|
BR0701 |
|
NP_697715.1 |
outer-membrane protein Omp25 |
Virulence factor |
SUBCELLULAR LOCATION: Outer membrane(Swiss-Prot: Q45689).
SIMILARITY: Belongs to the omp25/ropB family(Swiss-Prot: Q45689).
MUTATION: In contrast to WT B suis or Deltaomp31 B suis, Deltaomp25 B suis induced TNF-alpha production when phagocytosed by human macrophages. So Omp25 of B suis is involved in the negative regulation of TNF-alpha production upon infection of human macrophages [Ref6492:Jubier-Maurin et al., 2001].
To determine the role of Omp25 in virulence, mutants were created with Brucella abortus (BA25), Brucella melitensis (BM25), and Brucella ovis (BO25) which contain disruptions in the omp25 gene (Deltaomp25 mutants). BALBc mice infected with B abortus BA25 or B melitensis BM25 showed a significant decrease in mean CFUspleen at 18 and 4 weeks post-infection, respectively, when compared to the virulent parental strain. Mice infected with B ovis BO25 had significantly lower mean CFUspleen counts from 1 to 8 weeks post-infection, at which point the mutant was cleared from the spleens. Murine vaccination with either BM25 or the current caprine vaccine B melitensis strain Rev.1 resulted in more than a 2log (10) reduction in bacterial load following challenge with virulent B melitensis. Vaccination of mice with the B ovis mutant resulted in clearance of the challenge strain and provided 2.5log (10) greater protection against virulent B ovis than vaccine strain Rev.1. Based on these data, the B melitensis and B ovis Deltaomp25 mutants are interesting vaccine candidates that are currently under study in our laboratory for their safety and efficacy in small ruminants [Ref6492:Jubier-Maurin et al., 2001].
Although they are slightly attenuated, B abortus omp25 and omp22 mutants do not show the high level of attenuation and sensitivity to bactericidal peptides displayed by the bvrS and bvrR mutants [Ref6492:Jubier-Maurin et al., 2001]. B abortus mutants carrying Omp25 deletions do not show enrichment of underacylated LPS [Ref6492:Jubier-Maurin et al., 2001].
Brucella spp. omp25 deletion mutants are attenuated in mice, cattle and goats, showing the involvement of Brucella spp. Omp25 in virulence [Ref6492:Jubier-Maurin et al., 2001]. |
11447156
|
|
|
purN from Brucella suis 1330 |
Brucella suis 1330 |
1166372
|
|
161486698
|
BR0709 |
|
NP_697723.2 |
phosphoribosylglycinamide formyltransferase |
Virulence factor |
MUTATION: B. abortus purN gene is essential for intracellular growth in HeLa cells as shown from transposon mutagenesis study [Ref6469:Kim et al., 2003]. |
12761078
|
|
|
purM from Brucella suis 1330 |
Brucella suis 1330 |
1166373
|
|
23501597
|
BR0710 |
|
NP_697724.1 |
phosphoribosylaminoimidazole synthetase |
Virulence factor |
CATALYTIC ACTIVITY: ATP + 2-(formamido)-N(1)-(5-phospho-D-ribosyl)acetamidine = ADP + phosphate + 5-amino-1-(5-phospho-D-ribosyl)imidazole(Swiss-Prot: Q8G1K5).
PATHWAY: Nucleotide biosynthesis; IMP biosynthesis; 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide from N(2)-formyl-N(1)-(5-phospho-D-ribosyl)glycinamide: step 2(Swiss-Prot: Q8G1K5).
PATHWAY: Context: Purine biosynthesis(Swiss-Prot: Q8G1K5).
SUBCELLULAR LOCATION: Cytoplasm (By similarity)(Swiss-Prot: Q8G1K5).
SIMILARITY: Belongs to the AIR synthase family(Swiss-Prot: Q8G1K5).
MUTATION: B. abortus purM gene is essential for intracellular growth in HeLa cells as shown from transposon mutagenesis study [Ref6469:Kim et al., 2003]. |
12761078
|
|
|
galE from Brucella suis 1330 |
Brucella suis 1330 |
1166378
|
|
23501602
|
BR0715 |
|
NP_697729.1 |
epimerase/dehydratase family protein, putative |
Virulence factor |
FUNCTIONAL GROUP: a.a. metabolism, Unkown [Ref6462:Delrue et al., 2004].
FUNCTION: UDP-glucose 4-epimerase [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
glyA from Brucella suis 1330 |
Brucella suis 1330 |
1166430
|
|
23501652
|
BR0765 |
|
NP_697779.1 |
serine hydroxymethyltransferase |
Virulence factor |
FUNCTION: Interconversion of serine and glycine(Swiss-Prot: Q8G1F1).
CATALYTIC ACTIVITY: 5,10-methylenetetrahydrofolate + glycine + H(2)O = tetrahydrofolate + L-serine(Swiss-Prot: Q8G1F1).
COFACTOR: Pyridoxal phosphate (By similarity)(Swiss-Prot: Q8G1F1).
PATHWAY: Key enzyme in the biosynthesis of purines, lipids, hormones and other components(Swiss-Prot: Q8G1F1).
SUBUNIT: Homotetramer (By similarity)(Swiss-Prot: Q8G1F1).
SUBCELLULAR LOCATION: Cytoplasm (By similarity)(Swiss-Prot: Q8G1F1).
SIMILARITY: Belongs to the SHMT family(Swiss-Prot: Q8G1F1).
MUTATION: A study with miniTn5 mutants of B. suis constitutively expressing gfp indicates that B. suis glyA gene is required for intracellular multiplication in human macrophage THP-1 cells [Ref412:Kohler et al., 2002]. |
12438693
|
|
|
purL from Brucella suis 1330 |
Brucella suis 1330 |
1166505
|
|
23501724
|
BR0837 |
|
NP_697851.1 |
phosphoribosylformylglycinamidine synthase II |
Virulence factor |
CATALYTIC ACTIVITY: ATP + N(2)-formyl-N(1)-(5-phospho-D-ribosyl)glycinamide + L-glutamine + H(2)O = ADP + phosphate + 2-(formamido)-N(1)-(5-phospho-D-ribosyl)acetamidine + L-glutamate(Swiss-Prot: Q8G183).
PATHWAY: Nucleotide biosynthesis; IMP biosynthesis; 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide from N(2)-formyl-N(1)-(5-phospho-D-ribosyl)glycinamide: step 1(Swiss-Prot: Q8G183).
PATHWAY: Context: Purine biosynthesis(Swiss-Prot: Q8G183).
SUBUNIT: Heterodimer of two subunits, purQ and purL(Swiss-Prot: Q8G183).
SUBCELLULAR LOCATION: Cytoplasm (By similarity)(Swiss-Prot: Q8G183).
SIMILARITY: Belongs to the FGAMS family(Swiss-Prot: Q8G183).
MUTATION: Brucella abortus 2308 derivatives with mini-Tn5 insertions in purE, purL, and purD display significant attenuation in the BALBc mouse model. It confirms the importance of the purine biosynthesis pathways for the survival and replication of the brucellae in host macrophages [Ref6485:Alcantara et al., 2004]. Studies with B melitensis purE and B abortus purL mutants, which are purine auxotrophs, and B suis aroC mutants, which can not synthesize aromatic amino acids, indicate that the brucellae also face signicant nutrient limitation during their prolonged residence in host macrophages [Ref6485:Alcantara et al., 2004]. |
15271960
|
|
|
tig from Brucella suis 1330 |
Brucella suis 1330 |
1166567
|
|
23501784
|
BR0898 |
|
NP_697911.1 |
trigger factor |
Virulence factor |
FUNCTION: Involved in protein export. Acts as a chaperone by maintaining the newly synthesized protein in an open conformation (By similarity)(Swiss-Prot: Q8G129).
SIMILARITY: Belongs to the FKBP-type PPIase family. Tig subfamily(Swiss-Prot: Q8G129).
SIMILARITY: Contains 1 PPIase FKBP-type domain(Swiss-Prot: Q8G129).
MUTATION: tig encodes for Trigger factor that helps protein folding and secretion. It is one of the attenuated Signature-Tagged Mutagenesis mutants of Brucella melitensis identified during the acute phase of infection in mice [Ref6480:Lestrate et al., 2003]. |
14638795
|
|
|
dsbA from Brucella suis 1330 |
Brucella suis 1330 |
1166578
|
|
23501795
|
BR0909 |
|
NP_697922.1 |
outer membrane protein, putative |
Virulence factor |
FUNCTIONAL GROUP: Oxidoreduction [Ref6462:Delrue et al., 2004].
FUNCTION: Disulfide bond formation protein [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
amiC from Brucella suis 1330 |
Brucella suis 1330 |
1166584
|
|
23501801
|
BR0915 |
|
NP_697928.1 |
N-acetylmuramoyl-L-alanine amidase, family 3 |
Virulence factor |
FUNCTIONAL GROUP: "Classical virulence factors", Envelope molecules, peptidoglycan [Ref6462:Delrue et al., 2004].
FUNCTION: Cell-wall hydrolysis [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
nifS from Brucella suis 1330 |
Brucella suis 1330 |
1166599
|
|
23501814
|
BR0930 |
|
NP_697941.1 |
cysteine desulfurase, putative |
Virulence factor |
FUNCTIONAL GROUP: Nitrogen metabolism [Ref6462:Delrue et al., 2004].
FUNCTION: nitrogenase cofactor synthesis protein nifS [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Macrophages [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
dsbA from Brucella suis 1330 |
Brucella suis 1330 |
1166602
|
|
23501817
|
BR0933 |
|
NP_697944.1 |
hypothetical protein |
Virulence factor |
FUNCTIONAL GROUP: Oxidoreduction [Ref6462:Delrue et al., 2004].
FUNCTION: Disulfide bond formation protein [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
artI from Brucella suis 1330 |
Brucella suis 1330 |
1166625
|
|
23501838
|
BR0955 |
|
NP_697965.1 |
amino acid ABC transporter, periplasmic amino acid-binding protein |
Virulence factor |
FUNCTIONAL GROUP: a.a. metabolism, Transport [Ref6462:Delrue et al., 2004].
FUNCTION: Arginine transport system [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Differential fluorescence induction [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
wbdA from Brucella suis 1330 |
Brucella suis 1330 |
1166655
|
|
23501863
|
BR0982 |
|
NP_697990.1 |
glycosyl transferase, group 1 family protein |
Virulence factor |
FUNCTIONAL GROUP: "Classical virulence factors", Envelope molecules, Lipopolysaccharide [Ref6462:Delrue et al., 2004].
FUNCTION: O-chain biosynthesis [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Macrophages [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
glnA from Brucella suis 1330 |
Brucella suis 1330 |
1166677
|
|
23501884
|
BR1004 |
|
NP_698011.1 |
glutamine synthetase, type I |
Virulence factor |
MUTATION: A study with miniTn5 mutants of B. suis constitutively expressing gfp indicates that B. suis glnA gene is required for intracellular multiplication in human macrophage THP-1 cells [Ref412:Kohler et al., 2002]. |
12438693
|
|
|
cysK from Brucella suis 1330 |
Brucella suis 1330 |
1166727
|
|
23501931
|
BR1053 |
|
NP_698058.1 |
cysteine synthase A |
Virulence factor |
FUNCTIONAL GROUP: a.a. metabolism, Synthesis [Ref6462:Delrue et al., 2004].
FUNCTION: Cys. synthesis [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
caiB from Brucella suis 1330 |
Brucella suis 1330 |
1166760
|
|
23501962
|
BR1084 |
|
NP_698089.1 |
CAIB/BAIF family protein |
Virulence factor |
FUNCTIONAL GROUP: Oxidoreduction [Ref6462:Delrue et al., 2004].
FUNCTION: CAIB/BAIF family [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Macrophages [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
uvrA from Brucella suis 1330 |
Brucella suis 1330 |
1166780
|
|
23501982
|
BR1104 |
|
NP_698109.1 |
excinuclease ABC subunit A |
Virulence factor |
FUNCTION: The UvrABC repair system catalyzes the recognition and processing of DNA lesions. UvrA is an ATPase and a DNA-binding protein. A damage recognition complex composed of 2 uvrA and 2 uvrB subunits scans DNA for abnormalities. When the presence of a lesion has been verified by uvrB, the uvrA molecules dissociate (By similarity)(Swiss-Prot: Q8G0I9).
SUBUNIT: Forms a heterotetramer with uvrB during the search for lesions (By similarity)(Swiss-Prot: Q8G0I9).
SUBCELLULAR LOCATION: Cytoplasm (By similarity)(Swiss-Prot: Q8G0I9).
SIMILARITY: Belongs to the ABC transporter family. UvrA subfamily(Swiss-Prot: Q8G0I9).
SIMILARITY: Contains 2 ABC transporter domains(Swiss-Prot: Q8G0I9).
MUTATION: B. abortus urvA and recA mutants exhibited greater sensitivity than the wild-type strain. Mutant strains carrying inactivated uvrA genes are typically less sensitive than recA mutants because there is only the loss of the nucleotide excision repair system, just one subset of the larger repair networks. However, it was found that the recA mutant conferred only a modest sensitivity to UV, substantially less sensitive than the uvrA mutant. High basal recA expression was observed in the uvrA repair mutant. The B abortus recA mutant exhibited a nearly fourfold decline in survival to murine peritoneal macrophages but nominal sensitivity for the uvrA and radA repair mutants [Ref6493:Roux et al., 2006]. |
16816190
|
|
|
lon from Brucella suis 1330 |
Brucella suis 1330 |
1166782
|
|
23501984
|
BR1106 |
|
NP_698111.1 |
ATP-dependent protease La |
Virulence factor |
FUNCTION: Degrades short-lived regulatory and abnormal proteins in presence of ATP. Hydrolyzes two ATPs for each peptide bond cleaved in the protein substrate (By similarity)(Swiss-Prot: Q8G0I7).
CATALYTIC ACTIVITY: Hydrolysis of proteins in presence of ATP(Swiss-Prot: Q8G0I7).
SUBUNIT: Homotetramer (By similarity)(Swiss-Prot: Q8G0I7).
SUBCELLULAR LOCATION: Cytoplasm (By similarity)(Swiss-Prot: Q8G0I7).
SIMILARITY: Belongs to the peptidase S16 family(Swiss-Prot: Q8G0I7).
SIMILARITY: Contains 1 Lon domain(Swiss-Prot: Q8G0I7).
MUTATION: In contrast to the parent strain, the Brucella abortus lon mutant, was impaired in its capacity to form isolated colonies on solid medium at 41 degrees C and displayed an increased sensitivity to killing by puromycin and H2O2. Brucella abortus Lon homologue functions as a stress response protease that is required for wild-type virulence during the initial stages of infection in the mouse model, but is not essential for the establishment and maintenance of chronic infection in this host [Ref6494:Robertson et al., 2000].
Both single lon or clpA mutations had comparable effects on growth inhibition, suggesting that the concerned proteases Lon and ClpAP both degrade a number of specific proteins, but are also both involved in general degradation of abnormal proteins. Compared to the single mutants, the double mutant lon clpA was highly sensitive to canavanine. One possible explanation for this observation is that both proteases can substitute for each other to a large extent during bacterial growth. Hence, simultaneous inactivation or decrease in activation of both proteases, either by direct mutation or by elimination of the regulatory component ClpA, strongly increased growth inhibition [Ref6494:Robertson et al., 2000]. |
10672180
|
|
|
hfq from Brucella suis 1330 |
Brucella suis 1330 |
1166787
|
|
23501989
|
BR1111 |
|
NP_698116.1 |
RNA-binding protein Hfq |
Virulence factor |
FUNCTION: RNA-binding protein that stimulates the elongation of poly(A) tails (By similarity)(Swiss-Prot: P0A3G8).
SIMILARITY: Belongs to the hfq family(Swiss-Prot: P0A3G8).
MUTATION: hfq encodes for the RNA binding protein host factor I (HF-I). The hfq knock out strain has been showed a reduced growth rate and is unable to utilize glucose as a sole carbon source[Ref6495:Sonnleitner et al., 2003].
hfq is required for the efficient translation of the stationary-phase sigma factor RpoS in many bacteria, and a Brucella abortus hfq mutant displays a phenotype in vitro, which suggests that it has a generalized defect in stationary-phase physiology. The inability of the B. abortus hfq mutant to survive and replicate in a wild-type manner in cultured murine macrophages, and the profound attenuation displayed by this strain and its B melitensis counterpart in experimentally infected animals indicate that stationary -phase physiology plays an essential role in the capacity of the brucellae to establish and maintain long-term intracellular residence in host macrophages [Ref6495:Sonnleitner et al., 2003].
In contrast to B abortus 2308, the isogenic hfq and bacA mutants remained in acidic, LAMP-1 phagosomes and failed to initiate intracellular replication [Ref6495:Sonnleitner et al., 2003].
A hfq mutant of B abortus was eliminated from mouse spleens more rapidly than the wild type [Ref6495:Sonnleitner et al., 2003]. |
14521880
|
|
|
ntrY from Brucella suis 1330 |
Brucella suis 1330 |
1166792
|
|
23501994
|
BR1116 |
|
NP_698121.1 |
nitrogen regulation protein NtrY |
Virulence factor |
MUTATION: The NtrY protein is a sensor of an ntr-related regulon which may be part of the glnALG operon. This mutant has a weakly attenuated phenotype (reduction of 1.2 log units versus the wild type at 48 h postinfection) which could be explained by a pleiotropic effect on the ntr regulon, since the ntrC mutant did not show such a phenotype [Ref6484:Foulongne et al., 2000]. |
10678941
|
|
|
ntrC from Brucella suis 1330 |
Brucella suis 1330 |
1166793
|
|
23501995
|
BR1117 |
|
NP_698122.1 |
nitrogen regulation protein NtrC |
Virulence factor |
MUTATION: ntrC encodes for a response regulator subfamily (NtrC). A B suis ntrC isogenic mutant was constructed which showed no significant differences in growth rates compared to the wild-type strain when grown at different temperatures in vitro. However, the mutant exhibited a reduction in metabolic activity in the presence of many amino acids. The mutation did not affect survival or multiplication of B suis in macrophages, but during the initial stages of infection in the murine brucellosis model, the ntrC mutant showed a reduced ability to multiply rapidly in splenic tissue [Ref6496:Dorrell et al., 1999]. |
10373105
|
|
|
ppiD from Brucella suis 1330 |
Brucella suis 1330 |
1166815
|
|
23502017
|
BR1139 |
|
NP_698144.1 |
rotamase family protein |
Virulence factor |
FUNCTIONAL GROUP: Stress proteins/Chaperones [Ref6462:Delrue et al., 2004].
FUNCTION: Rotamase D [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
uppS from Brucella suis 1330 |
Brucella suis 1330 |
1166834
|
|
23502036
|
BR1158 |
|
NP_698163.1 |
undecaprenyl diphosphate synthase |
Virulence factor |
FUNCTION: Generates undecaprenyl pyrophosphate (UPP) from isopentenyl pyrophosphate (IPP). UPP is the precursor of glycosyl carrier lipid in the biosynthesis of bacterial cell wall polysaccharide components such as peptidoglycan and lipopolysaccharide (By similarity)(Swiss-Prot: Q8G0D9).
CATALYTIC ACTIVITY: Di-trans,poly-cis-decaprenyl diphosphate + isopentenyl diphosphate = diphosphate + di-trans,poly-cis-undecaprenyl diphosphate(Swiss-Prot: Q8G0D9).
COFACTOR: Magnesium (By similarity)(Swiss-Prot: Q8G0D9).
SUBUNIT: Homodimer (By similarity)(Swiss-Prot: Q8G0D9).
SIMILARITY: Belongs to the UPP synthetase family(Swiss-Prot: Q8G0D9).
MUTATION: A study with miniTn5 mutants of B. suis constitutively expressing gfp indicates that B. suis uppS gene is required for intracellular multiplication in human macrophage THP-1 cells [Ref412:Kohler et al., 2002]. |
12438693
|
|
|
recA from Brucella suis 1330 |
Brucella suis 1330 |
1166878
|
|
23502079
|
BR1202 |
|
NP_698206.1 |
recombinase A |
Virulence factor |
FUNCTION: Can catalyze the hydrolysis of ATP in the presence of single-stranded DNA, the ATP-dependent uptake of single-stranded DNA by duplex DNA, and the ATP-dependent hybridization of homologous single-stranded DNAs. It interacts with lexA causing its activation and leading to its autocatalytic cleavage (By similarity)(Swiss-Prot: P65976).
SUBCELLULAR LOCATION: Cytoplasm (By similarity)(Swiss-Prot: P65976).
SIMILARITY: Belongs to the recA family(Swiss-Prot: P65976).
MUTATION: The RecA mutant was more sensitive than the parental strain to killing by MMS. When administered intraperitoneally to BALBc mice, numbers of bacteria per spleen were consistently lower in animals infected with the RecA mutant than with the parental strain. However, both the RecA mutant and parental strain persisted in mice through 100 days post-infection. These results indicate that RecA is not crucial for persistence of B abortus in mice [Ref6497:Halling, 2002].
The B abortus RecA mutant was virulent in mice, but its course of infection in mice differed from that of the parental strain. The infectious cycle of the parental strain in the mouse model was biphasic. During the rst week, there was an initial rise in cfu of B abortus 2308 in the spleen followed by a decrease during the second week. This phase was followed by a second phase in which B abortus S2308 persisted and slowly increased in numbers in the spleen . Though fewer RecA mutants were found in the spleens of mice infected intraperitoneally in the early stages of the infection and no large initial rise was seen, the same numbers were found as the parental strain 100 days post -infection. This suggests that collectively, different loci are involved to varying extents in the initial infection and the persistence phase [Ref6497:Halling, 2002].
|
12414170
|
|
|
rpoA from Brucella suis 1330 |
Brucella suis 1330 |
1166885
|
|
23502086
|
BR1209 |
|
NP_698213.1 |
DNA-directed RNA polymerase subunit alpha |
Virulence factor |
FUNCTION: DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates(Swiss-Prot: Q8G094).
CATALYTIC ACTIVITY: Nucleoside triphosphate + RNA(n) = diphosphate + RNA(n+1)(Swiss-Prot: Q8G094).
SUBUNIT: Homodimer. The RNAP catalytic core consists of 2 alpha, 1 beta, 1 beta' and 1 omega subunit. When a sigma factor is associated with the core the holoenzyme is formed, which can initiate transcription (By similarity)(Swiss-Prot: Q8G094).
DOMAIN: The N-terminal domain is essential for RNAP assembly and basal transcription, whereas the C-terminal domain is involved in interaction with transcriptional regulators and with upstream promoter elements (By similarity)(Swiss-Prot: Q8G094).
SIMILARITY: Belongs to the RNA polymerase alpha chain family(Swiss-Prot: Q8G094).
MUTATION: The rpoA gene codes for the essential alpha-subunit of the RNA polymerase. B. melitensis rpoA mutant was found by signature-tagged mutagenesis from a mouse infection model. This disruption leaves a partially functional protein, impaired for the activation of virB transcription, as demonstrated by the absence of induction of the virB promoter in the Tn5::rpoA background. RpoA is involved in virB regulation in vitro. The mutant (Tn5::rpoA) was more resistant to oxidative stress [Ref6480:Lestrate et al., 2003]. |
14638795
|
|
|
gloA from Brucella suis 1330 |
Brucella suis 1330 |
1166947
|
|
23502144
|
BR1268 |
|
NP_698271.1 |
lactoylglutathione lyase |
Virulence factor |
FUNCTIONAL GROUP: a.a. metabolism, Unkown [Ref6462:Delrue et al., 2004].
FUNCTION: Lactoylglutathione lyase (pyruvate metabolism) [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Differential fluorescence induction [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
cobB from Brucella suis 1330 |
Brucella suis 1330 |
1166977
|
|
23502172
|
BR1296 |
|
NP_698299.1 |
cobyrinic acid a,c-diamide synthase |
Virulence factor |
FUNCTION: Responsible for the amidation of carboxylic groups at position A and C of either cobyrinic acid or hydrogenobrynic acid. NH(2) groups are provided by glutamine, and one molecule of ATP is hydrogenolyzed for each amidation (By similarity)(Swiss-Prot: Q8G020).
PATHWAY: Cobalamin biosynthesis(Swiss-Prot: Q8G020).
SIMILARITY: Belongs to the cobB/cobQ family. CobB subfamily(Swiss-Prot: Q8G020).
MUTATION: 1,152 signature-tagged mutagenesis mutants of Brucella melitensis 16M were screened in a mouse model of infection. 36 of them to be attenuated in vivo. cobB is one of them [Ref6480:Lestrate et al., 2003]. |
14638795
|
|
|
aspB from Brucella suis 1330 |
Brucella suis 1330 |
1167060
|
|
23502249
|
BR1378 |
|
NP_698376.1 |
aminotransferase, class I |
Virulence factor |
FUNCTIONAL GROUP: a.a. metabolism, Unkown [Ref6462:Delrue et al., 2004].
FUNCTION: Aminotransferase [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Macrophages [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
ilvC from Brucella suis 1330 |
Brucella suis 1330 |
1167062
|
|
23502251
|
BR1380 |
|
NP_698378.1 |
ketol-acid reductoisomerase |
Virulence factor |
CATALYTIC ACTIVITY: (R)-2,3-dihydroxy-3-methylbutanoate + NADP(+) = (S)-2-hydroxy-2-methyl-3-oxobutanoate + NADPH(Swiss-Prot: Q8FZU1).
CATALYTIC ACTIVITY: (2R,3R)-2,3-dihydroxy-3-methylpentanoate + NADP(+) = (S)-2-hydroxy-2-ethyl-3-oxobutanoate + NADPH(Swiss-Prot: Q8FZU1).
PATHWAY: Amino-acid biosynthesis; L-isoleucine biosynthesis; L-isoleucine from 2-oxobutanoate: step 2(Swiss-Prot: Q8FZU1).
PATHWAY: Amino-acid biosynthesis; L-valine biosynthesis; L-valine from pyruvate: step 2(Swiss-Prot: Q8FZU1).
SIMILARITY: Belongs to the ketol-acid reductoisomerase family(Swiss-Prot: Q8FZU1).
MUTATION: ilvC is one of the 37 mutants with virulene defect, screened out from the signature- tagged miniTn5 library [Ref6480:Lestrate et al., 2003]. |
14638795
|
|
|
miaA from Brucella suis 1330 |
Brucella suis 1330 |
1167072
|
|
23502261
|
BR1390 |
|
NP_698388.1 |
tRNA delta(2)-isopentenylpyrophosphate transferase |
Virulence factor |
FUNCTION: Catalyzes the first step in the biosynthesis of 2-methylthio-N6-(delta(2)-isopentenyl)-adenosine (MS[2]I[6]A) adjacent to the anticodon of several tRNA species (By similarity)(Swiss-Prot: Q8CY40).
CATALYTIC ACTIVITY: Isopentenyl diphosphate + tRNA = diphosphate + tRNA containing 6-isopentenyladenosine(Swiss-Prot: Q8CY40).
SIMILARITY: Belongs to the IPP transferase family(Swiss-Prot: Q8CY40).
MUTATION: A study with miniTn5 mutants of B. suis constitutively expressing gfp indicates that B. suis miaA gene is required for intracellular multiplication in human macrophage THP-1 cells [Ref412:Kohler et al., 2002]. |
12438693
|
|
|
serB from Brucella suis 1330 |
Brucella suis 1330 |
1167073
|
|
23502262
|
BR1391 |
|
NP_698389.1 |
phosphoserine phosphatase |
Virulence factor |
MUTATION: A study with miniTn5 mutants of B. suis constitutively expressing gfp indicates that B. suis serB gene is required for intracellular multiplication in human macrophage THP-1 cells [Ref412:Kohler et al., 2002]. |
12438693
|
|
|
pncA from Brucella suis 1330 |
Brucella suis 1330 |
1167146
|
|
23502333
|
BR1464 |
|
NP_698460.1 |
pyrazinamidase/nicotinamidase |
Virulence factor |
MUTATION: Brucella abortus pnc mutant via mini-Tn5Km2 transposon mutagenesis has intracellular growth defect inside HeLa cells [Ref6469:Kim et al., 2003]. Nicotinamidasepyrazinamidase mutant (pncA mutant) of Brucella abortus failed to replicate in HeLa cells, and showed a lower rate of intracellular replication than that of wild-type strain in macrophages [Ref6469:Kim et al., 2003]. The pncA mutant was not co-localizing with either late endosomes or lysosomes. The pncA mutant showed a 1.5-log reduction of the number of bacteria isolated from mouse spleens after 10 weeks [Ref6469:Kim et al., 2003]. It indicates that the mutant has reduced virulence in mice. |
12761078
|
|
|
pncA from Brucella suis 1330 |
Brucella suis 1330 |
1167147
|
|
23502334
|
BR1465 |
|
NP_698461.1 |
hypothetical protein |
Virulence factor |
MUTATION: Brucella abortus pnc mutant via mini-Tn5Km2 transposon mutagenesis has intracellular growth defect inside HeLa cells [Ref6469:Kim et al., 2003]. Nicotinamidasepyrazinamidase mutant (pncA mutant) of Brucella abortus failed to replicate in HeLa cells, and showed a lower rate of intracellular replication than that of wild-type strain in macrophages [Ref6468:Kim et al., 2004]. The pncA mutant was not co-localizing with either late endosomes or lysosomes. The pncA mutant showed a 1.5-log reduction of the number of bacteria isolated from mouse spleens after 10 weeks [Ref6468:Kim et al., 2004]. It indicates that the mutant has reduced virulence in mice. |
12761078
15135535
|
|
|
aspC from Brucella suis 1330 |
Brucella suis 1330 |
1167178
|
|
23502364
|
BR1495 |
|
NP_698491.1 |
aspartate aminotransferase |
Virulence factor |
MUTATION: aspC encodes for an aminotransferase. B.abortus aspC mutant obtained from randomized miniTn5Km2 transposon mutagenesis showed decreased intracellular survival inside HeLa cells. So B. abortus aspC gene is essential for HeLa cell intracellular growth [Ref6469:Kim et al., 2003]. |
12761078
|
|
|
lysR from Brucella suis 1330 |
Brucella suis 1330 |
1167181
|
|
23502367
|
BR1498 |
|
NP_698494.1 |
transcriptional regulator, LysR family |
Virulence factor |
FUNCTIONAL GROUP: "Classical virulence factors", Secretion of transport system, Flagella [Ref6462:Delrue et al., 2004].
FUNCTION: Transcriptional regulator [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
pth from Brucella suis 1330 |
Brucella suis 1330 |
1167219
|
|
23502404
|
BR1536 |
|
NP_698531.1 |
peptidyl-tRNA hydrolase |
Virulence factor |
FUNCTION: The natural substrate for this enzyme may be peptidyl-tRNAs which drop off the ribosome during protein synthesis (By similarity)(Swiss-Prot: P65864).
CATALYTIC ACTIVITY: N-substituted aminoacyl-tRNA + H(2)O = N-substituted amino acid + tRNA(Swiss-Prot: P65864).
SUBUNIT: Monomer (By similarity)(Swiss-Prot: P65864).
SUBCELLULAR LOCATION: Cytoplasm (By similarity)(Swiss-Prot: P65864).
SIMILARITY: Belongs to the PTH family(Swiss-Prot: P65864).
MUTATION: pth encodes for a peptidyl tRNA hydrolase. Transposon insertion in pth has a polar effect on dugA expression and that the pth/dugA mutant is deficient in iron assimilation because of altered expression of the dugA gene. Only minor difference in intracellular growth in bovine macrophages and HeLa cells between the pth/dugA mutant and wild-type strains was observed [Ref6498:Danese et al., 2004]. |
15385478
|
|
|
leuA from Brucella suis 1330 |
Brucella suis 1330 |
1167249
|
|
161486694
|
BR1566 |
|
NP_698557.2 |
2-isopropylmalate synthase |
Virulence factor |
FUNCTION: Catalyzes the condensation of the acetyl group of acetyl-CoA with 3-methyl-2-oxobutanoate (2-oxoisovalerate) to form 3-carboxy-3-hydroxy-4-methylpentanoate (2-isopropylmalate)(Swiss-Prot: Q8FZC4).
CATALYTIC ACTIVITY: Acetyl-CoA + 3-methyl-2-oxobutanoate + H(2)O = (2S)-2-isopropylmalate + CoA(Swiss-Prot: Q8FZC4).
PATHWAY: Amino-acid biosynthesis; L-leucine biosynthesis; L-leucine from 3-methyl-2-oxobutanoate: step 1(Swiss-Prot: Q8FZC4).
SUBUNIT: Homotetramer (By similarity)(Swiss-Prot: Q8FZC4).
SIMILARITY: Belongs to the alpha-IPM synthetase/homocitrate synthase family. LeuA type 2 subfamily(Swiss-Prot: Q8FZC4).
MUTATION: leuA is a B. suis gene identified by signature-tagged mutagenesis. It is attenuated inside THP1 macrophage cell line. |
|
|
|
dsbB from Brucella suis 1330 |
Brucella suis 1330 |
1167334
|
|
23502502
|
BR1642 |
|
NP_698629.1 |
disulfide bond formation protein B, putative |
Virulence factor |
FUNCTIONAL GROUP: Oxidoreduction [Ref6462:Delrue et al., 2004].
FUNCTION: Disulfide bond formation protein [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Mice, Macrophages [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
alkA from Brucella suis 1330 |
Brucella suis 1330 |
1167338
|
|
23502506
|
BR1646 |
|
NP_698633.1 |
base-excision DNA repair protein |
Virulence factor |
FUNCTIONAL GROUP: DNA/RNA metabolism, Repair [Ref6462:Delrue et al., 2004].
FUNCTION: HhH-GPD superfamily base excision DNA repair [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
macA from Brucella suis 1330 |
Brucella suis 1330 |
1167364
|
|
23502529
|
BR1671 |
|
NP_698656.1 |
HlyD family secretion protein |
Virulence factor |
FUNCTIONAL GROUP: "Classical virulence factors", Secretion of transport system, Transpter [Ref6462:Delrue et al., 2004].
FUNCTION: Macrolide efflux [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
dut from Brucella suis 1330 |
Brucella suis 1330 |
1167368
|
|
23502533
|
BR1675 |
|
NP_698660.1 |
deoxyuridine 5'-triphosphate nucleotidohydrolase |
Virulence factor |
FUNCTION: This enzyme is involved in nucleotide metabolism: it produces dUMP, the immediate precursor of thymidine nucleotides and it decreases the intracellular concentration of dUTP so that uracil cannot be incorporated into DNA (By similarity)(Swiss-Prot: P64005).
CATALYTIC ACTIVITY: dUTP + H(2)O = dUMP + diphosphate(Swiss-Prot: P64005).
PATHWAY: De novo synthesis of thymidylate(Swiss-Prot: P64005).
SIMILARITY: Belongs toMUTATION: A study with miniTn5 mutants of B. suis constitutively expressing gfp indicates that B. suis dut gene is required for intracellular multiplication in human macrophage THP-1 cells [Ref412:Kohler et al., 2002]. the dUTPase family(Swiss-Prot: P64005). |
12438693
|
|
|
ansC from Brucella suis 1330 |
Brucella suis 1330 |
1167369
|
|
23502534
|
BR1676 |
|
NP_698661.1 |
transcriptional regulator, AsnC family |
Virulence factor |
FUNCTIONAL GROUP: "Classical virulence factors", Secretion of transport system, Flagella [Ref6462:Delrue et al., 2004].
FUNCTION: Transcriptional regulator [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
purE from Brucella suis 1330 |
Brucella suis 1330 |
1167437
|
|
23502601
|
BR1744 |
|
NP_698728.1 |
phosphoribosylaminoimidazole carboxylase, catalytic subunit |
Virulence factor |
FUNCTION: This subunit can alone transform AIR to CAIR, but in association with purK, which possesses an ATPase activity, an enzyme complex is produced which is capable of converting AIR to CAIR efficiently under physiological condition (By similarity)(Swiss-Prot: Q8FYW3).
CATALYTIC ACTIVITY: 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxylate = 5-amino-1-(5-phospho-D-ribosyl)imidazole + CO(2)(Swiss-Prot: Q8FYW3).
PATHWAY: Nucleotide biosynthesis; IMP biosynthesis; 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide from N(2)-formyl-N(1)-(5-phospho-D-ribosyl)glycinamide: step 3(Swiss-Prot: Q8FYW3).
PATHWAY: Context: Purine biosynthesis(Swiss-Prot: Q8FYW3).
SUBUNIT: Homooctamer (By similarity)(Swiss-Prot: Q8FYW3).
SIMILARITY: Belongs to the AIR carboxylase family(Swiss-Prot: Q8FYW3).
MUTATION: Brucella abortus 2308 derivatives with mini-Tn5 insertions in purE, purL, and purD display significant attenuation in the BALBc mouse model. It confirms the importance of the purine biosynthesis pathways for the survival and replication of the brucellae in host macrophages [Ref6485:Alcantara et al., 2004]. The purE mutant has reduced survival in murine macrophages and reduced virulence in mice [Ref6485:Alcantara et al., 2004].
A purE gene deletion mutant (purE201) of B melitensis was constructed as a potentially useful vaccine for humans and animals. At necropsy, bacteria were present in mammary lymph nodes or spleen of 33 of goats given virulent 16M but in none of goats given the purE mutant. The purE mutation of B melitensis 16M was stable and that the vaccine could be differentiated from wild-type strains by hybridization, purine auxotrophy, and kanamycin resistance. Mice clear the identical purE mutant strain from their spleens in only 8 weeks but remain infected with B. melitensis 16M for at least 3 months [Ref6485:Alcantara et al., 2004]. |
15271960
|
|
|
pyc from Brucella suis 1330 |
Brucella suis 1330 |
1167474
|
|
23502636
|
BR1781 |
|
NP_698763.1 |
pyruvate carboxylase |
Virulence factor |
MUTATION: pyc is one B. suis gene identified by signature-tagged mutagenesis. It is essential for survival and mulitplication in macrophages [Ref6484:Foulongne et al., 2000]. |
10678941
|
|
|
livH from Brucella suis 1330 |
Brucella suis 1330 |
1167484
|
|
23502645
|
BR1791 |
|
NP_698772.1 |
branched-chain amino acid ABC transporter, permease protein |
Virulence factor |
FUNCTIONAL GROUP: a.a. metabolism, Transport [Ref6462:Delrue et al., 2004].
FUNCTION: Branched as transport system [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Differential fluorescence induction [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
purH from Brucella suis 1330 |
Brucella suis 1330 |
1167509
|
|
23502669
|
BR1816 |
|
NP_698796.1 |
bifunctional phosphoribosylaminoimidazolecarboxamide formyltransferase/IMP cyclohydrolase |
Virulence factor |
CATALYTIC ACTIVITY: 10-formyltetrahydrofolate + 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide = tetrahydrofolate + 5-formamido-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide(Swiss-Prot: P67540).
CATALYTIC ACTIVITY: IMP + H(2)O = 5-formamido-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide(Swiss-Prot: P67540).
PATHWAY: Nucleotide biosynthesis; IMP biosynthesis; 5-formamido-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide from 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide (10-formyl THF route): single step(Swiss-Prot: P67540).
PATHWAY: Nucleotide biosynthesis; IMP biosynthesis; IMP from 5-formamido-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide: single step [final step](Swiss-Prot: P67540).
PATHWAY: Context: Purine biosynthesis(Swiss-Prot: P67540).
DOMAIN: The IMP cyclohydrolase activity resides in the N-terminal region (By similarity)(Swiss-Prot: P67540).
SIMILARITY: Belongs to the purH family(Swiss-Prot: P67540).
MUTATION: B. abortus mutant with mini-Tn5-disrupted purH displays nutritional defects in vitro [Ref6485:Alcantara et al., 2004]. |
15271960
|
|
|
leuC from Brucella suis 1330 |
Brucella suis 1330 |
1167606
|
|
23502757
|
BR1906 |
|
NP_698884.1 |
isopropylmalate isomerase large subunit |
Virulence factor |
FUNCTION: Catalyzes the isomerization between 2-isopropylmalate and 3-isopropylmalate, via the formation of 2-isopropylmaleate(Swiss-Prot: Q8FYG9).
CATALYTIC ACTIVITY: (2R,3S)-3-isopropylmalate = (2S)-2-isopropylmaleate + H(2)O(Swiss-Prot: Q8FYG9).
CATALYTIC ACTIVITY: (2S)-2-isopropylmaleate + H(2)O = 3-hydroxy-4-methyl-3-carboxypentanoate(Swiss-Prot: Q8FYG9).
COFACTOR: Binds 1 4Fe-4S cluster per subunit (By similarity)(Swiss-Prot: Q8FYG9).
PATHWAY: Amino-acid biosynthesis; L-leucine biosynthesis; L-leucine from 3-methyl-2-oxobutanoate: step 2(Swiss-Prot: Q8FYG9).
SUBUNIT: Heterodimer of leuC and leuD (By similarity)(Swiss-Prot: Q8FYG9).
SIMILARITY: Belongs to the aconitase/IPM isomerase family. LeuC type 1 subfamily(Swiss-Prot: Q8FYG9).
MUTATION: A study with miniTn5 mutants of B. suis constitutively expressing gfp indicates that B. suis leuC gene is required for intracellular multiplication in human macrophage THP-1 cells [Ref412:Kohler et al., 2002]. |
12438693
|
|
|
rplS from Brucella suis 1330 |
Brucella suis 1330 |
1167607
|
|
23502758
|
BR1907 |
|
NP_698885.1 |
50S ribosomal protein L19 |
Virulence factor |
FUNCTION: This protein is located at the 30S-50S ribosomal subunit interface and may play a role in the structure and function of the aminoacyl-tRNA binding site (By similarity)(Swiss-Prot: P66079).
SIMILARITY: Belongs to the ribosomal protein L19P family(Swiss-Prot: P66079).
MUTATION: rplS is involved in traanslation. B. abortus rplS mutant by the mini-Tn5 disruption displays nutritional defects in vitro [Ref6485:Alcantara et al., 2004]. |
15271960
|
|
|
omp19 from Brucella suis 1330 |
Brucella suis 1330 |
1167630
|
|
23502780
|
BR1930 |
|
NP_698907.1 |
lipoprotein Omp19 |
Virulence factor |
SUBCELLULAR LOCATION: Outer membrane; lipid-anchor(Swiss-Prot: P0A3P2).
MISCELLANEOUS: Elicits an immune response in humans, mice, sheep and goats infected with B.melitensis or B.abortus, but not in B.abortus-infected cattle(Swiss-Prot: P0A3P2).
SIMILARITY: Belongs to the rhizobiaceae omp19 lipoprotein family(Swiss-Prot: P0A3P2).
MUTATION: Omp19 is an immunoreactive outer membrane lipoprotein. Significantly fewer brucellae were recovered from the spleens of mice infected with the omp19 mutant than from those of mice infected with the parent strain at 4 and 8 weeks postinfection. The omp19 mutant exhibited an increase in sensitivity to the polycation polymyxin B and to sodium deoxycholate. These results indicate that inactivation of the omp19 gene alters the outer membrane properties of B abortus [Ref6473:Tibor et al., 2002]. |
12228280
|
|
|
cysK from Brucella suis 1330 |
Brucella suis 1330 |
1167668
|
|
0
|
BR1967 |
|
- |
pseudo |
Virulence factor |
FUNCTIONAL GROUP: a.a. metabolism, Synthesis [Ref6462:Delrue et al., 2004].
FUNCTION: Cys. synthesis [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
lysA from Brucella suis 1330 |
Brucella suis 1330 |
1167684
|
|
23502831
|
BR1983 |
|
NP_698958.1 |
diaminopimelate decarboxylase |
Virulence factor |
MUTATION: A study with miniTn5 mutants of B. suis constitutively expressing gfp indicates that B. suis lysA gene is required for intracellular multiplication in human macrophage THP-1 cells [Ref412:Kohler et al., 2002]. |
12438693
|
|
|
hpt from Brucella suis 1330 |
Brucella suis 1330 |
1167686
|
|
23502833
|
BR1985 |
|
NP_698960.1 |
hypoxanthine-guanine phosphoribosyltransferase |
Virulence factor |
FUNCTIONAL GROUP: DNA/RNA metabolism, Synthesis [Ref6462:Delrue et al., 2004].
FUNCTION: Purines synthesis [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
hisC from Brucella suis 1330 |
Brucella suis 1330 |
1167688
|
|
23502835
|
BR1987 |
|
NP_698962.1 |
histidinol-phosphate aminotransferase |
Virulence factor |
CATALYTIC ACTIVITY: L-histidinol phosphate + 2-oxoglutarate = 3-(imidazol-4-yl)-2-oxopropyl phosphate + L-glutamate(Swiss-Prot: Q8FY98).
COFACTOR: Pyridoxal phosphate (By similarity)(Swiss-Prot: Q8FY98).
PATHWAY: Amino-acid biosynthesis; L-histidine biosynthesis; L-histidine from 5-phospho-alpha-D-ribose 1-diphosphate: step 7(Swiss-Prot: Q8FY98).
SUBUNIT: Homodimer (By similarity)(Swiss-Prot: Q8FY98).
SIMILARITY: Belongs to the class-II pyridoxal-phosphate-dependent aminotransferase family. Histidinol-phosphate aminotransferase subfamily(Swiss-Prot: Q8FY98).
MUTATION: hisC encodes for histidinol phosphate transaminase. Brucella hisC mutant showed very little reduction in number by 2 weeks post-inoculation, but was reduced by 8 weeks. |
|
|
|
hisF from Brucella suis 1330 |
Brucella suis 1330 |
1167788
|
|
23502933
|
BR2085 |
|
NP_699060.1 |
imidazole glycerol phosphate synthase subunit HisF |
Virulence factor |
FUNCTION: IGPS catalyzes the conversion of PRFAR and glutamine to IGP, AICAR and glutamate. The hisF subunit catalyzes the cyclization activity that produces IGP and AICAR from PRFAR using the ammonia provided by the hisH subunit (By similarity)(Swiss-Prot: Q8FY07).
CATALYTIC ACTIVITY: 5-[(5-phospho-1-deoxyribulos-1-ylamino)methylideneamino]-1-(5-phosphoribosyl)imidazole-4-carboxamide + L-glutamine = imidazole-glycerol phosphate + 5-aminoimidazol-4-carboxamide ribonucleotide + L-glutamate + H(2)O(Swiss-Prot: Q8FY07).
PATHWAY: Amino-acid biosynthesis; L-histidine biosynthesis; L-histidine from 5-phospho-alpha-D-ribose 1-diphosphate: step 5(Swiss-Prot: Q8FY07).
SUBUNIT: Heterodimer of hisH and hisF (By similarity)(Swiss-Prot: Q8FY07).
SUBCELLULAR LOCATION: Cytoplasm (By similarity)(Swiss-Prot: Q8FY07).
SIMILARITY: Belongs to the hisA/hisF family(Swiss-Prot: Q8FY07).
MUTATION: A study with miniTn5 mutants of B. suis constitutively expressing gfp indicates that B. suis hisF gene is required for intracellular multiplication in human macrophage THP-1 cells [Ref412:Kohler et al., 2002]. |
12438693
|
|
|
bvrR from Brucella suis 1330 |
Brucella suis 1330 |
1167793
|
|
23502938
|
BR2090 |
|
NP_699065.1 |
DNA-binding response regulator BvrR, putative |
Virulence factor |
MUTATION: The two-component BvrSBvrR system is essential for Brucella abortus virulence. Disruption of BvrSBvrR damages the outer membrane, thus contributing to the severe attenuation manifested by bvrS and bvrR mutants. The bvrS and bvrR mutants are avirulent in mice, show reduced invasiveness to epithelial cells and macrophages, and are incapable of inhibiting lysosome fusion and replicating intracellularly [Ref6499:Guzman-Verri et al., 2002].
Mutations in the bvrR or bvrS genes hamper the penetration of B abortus in non-phagocytic cells and impairs intracellular trafficking and virulence. BvrRBvrS mutants do not recruit small GTPases of the Rho subfamily required for actin polymerization and penetration to cells. Dysfunction of the BvrRBvrS system alters the outer membrane permeability, the expression of several group 3 outer membrane proteins and the pattern of lipid A acylation. Constructs of virulent B abortus chimeras containing heterologous LPS from the bvrS(-) mutant demonstrated an altered permeability to cationic peptides similar to that of the BvrRBvrS mutants. It is hypothesized that the Brucella BvrRBvrS is a system devoted to the homeostasis of the outer membrane and, therefore in the interface for cell invasion and mounting the required structures for intracellular parasitism [Ref6499:Guzman-Verri et al., 2002].
In contrast to S2308 and S19, bvrS and bvrR mutant strains poorly invade HeLa cells and are rapidly targeted to cathepsin D- containing compartments [Ref6499:Guzman-Verri et al., 2002].
B abortus bvrS bvrR mutants display reduced invasiveness and virulence [Ref6499:Guzman-Verri et al., 2002].
Brucella bvrS and bvrR null mutants are defective in several outer membrane proteins, mainly Omp3a (former Omp25) and Omp3b as well as in the structure of the LPS molecule, but the O chain seems to be intact [Ref6499:Guzman-Verri et al., 2002].
Because bvrR and bvrS mutants are also altered in cell-surface hydrophobicity, permeability, and sensitivity to surface- targeted bactericidal peptides, it is proposed that BvrRBvrS controls cell envelope changes necessary to transit between extracellular and intracellular environments [Ref6499:Guzman-Verri et al., 2002].
BvrR/BvrS mutants are avirulent in mice, show reduced invasiveness in cells, and are unable to inhibit lysosome fusion and to replicate intracellularly [Ref6499:Guzman-Verri et al., 2002]. |
12218183
|
|
|
bvrS from Brucella suis 1330 |
Brucella suis 1330 |
1167794
|
|
23502939
|
BR2091 |
|
NP_699066.1 |
sensor histidine kinase BvrS, putative |
Virulence factor |
MUTATION: The two-component BvrSBvrR system is essential for Brucella abortus virulence. Disruption of BvrSBvrR damages the outer membrane, thus contributing to the severe attenuation manifested by bvrS and bvrR mutants. The bvrS and bvrR mutants are avirulent in mice, show reduced invasiveness to epithelial cells and macrophages, and are incapable of inhibiting lysosome fusion and replicating intracellularly [Ref6499:Guzman-Verri et al., 2002].
Mutations in the bvrR or bvrS genes hamper the penetration of B abortus in non-phagocytic cells and impairs intracellular trafficking and virulence. BvrRBvrS mutants do not recruit small GTPases of the Rho subfamily required for actin polymerization and penetration to cells. Dysfunction of the BvrRBvrS system alters the outer membrane permeability, the expression of several group 3 outer membrane proteins and the pattern of lipid A acylation. Constructs of virulent B abortus chimeras containing heterologous LPS from the bvrS(-) mutant demonstrated an altered permeability to cationic peptides similar to that of the BvrRBvrS mutants. It is hypothesized that the Brucella BvrRBvrS is a system devoted to the homeostasis of the outer membrane and, therefore in the interface for cell invasion and mounting the required structures for intracellular parasitism [Ref6499:Guzman-Verri et al., 2002].
In contrast to S2308 and S19, bvrS and bvrR mutant strains poorly invade HeLa cells and are rapidly targeted to cathepsin D- containing compartments [Ref6499:Guzman-Verri et al., 2002].
B abortus bvrS bvrR mutants display reduced invasiveness and virulence [Ref6499:Guzman-Verri et al., 2002].
Brucella bvrS and bvrR null mutants are defective in several outer membrane proteins, mainly Omp3a (former Omp25) and Omp3b as well as in the structure of the LPS molecule, but the O chain seems to be intact [Ref6499:Guzman-Verri et al., 2002].
Because bvrR and bvrS mutants are also altered in cell-surface hydrophobicity, permeability, and sensitivity to surface- targeted bactericidal peptides, it is proposed that BvrRBvrS controls cell envelope changes necessary to transit between extracellular and intracellular environments [Ref6499:Guzman-Verri et al., 2002].
BvrR/BvrS mutants are avirulent in mice, show reduced invasiveness in cells, and are unable to inhibit lysosome fusion and to replicate intracellularly [Ref6499:Guzman-Verri et al., 2002]. |
12218183
|
|
|
dnaK from Brucella suis 1330 |
Brucella suis 1330 |
1167828
|
|
23502973
|
BR2125 |
|
NP_699100.1 |
molecular chaperone DnaK |
Virulence factor |
FUNCTION: Acts as a chaperone (By similarity)(Swiss-Prot: Q8FXX2).
INDUCTION: By stress conditions e.g. heat shock (By similarity)(Swiss-Prot: Q8FXX2).
SIMILARITY: Belongs to the heat shock protein 70 family(Swiss-Prot: Q8FXX2).
MUTATION: The heat shock protein DnaK is essential for intramacrophagic replication of Brucella suis. The replacement of the stress-inducible, native dnaK promoter of B suis by the promoter of the constitutively expressed bla gene resulted in temperature-independent synthesis of DnaK. In contrast to a dnaK null mutant, this strain grew at 37 degrees C, with a thermal cutoff at 39 degrees C However, the constitutive dnaK mutant, which showed high sensitivity to H(2)O(2)-mediated stress , failed to multiply in murine macrophage-like cells and was rapidly eliminated in a mouse model of infection, adding strong arguments that stress-mediated and heat shock promoter-dependent induction of dnaK is a crucial event in the intracellular replication of B suis [Ref6500:Köhler et al., 2002].
Mutation studies indicated that DnaK, but not DnaJ, was required for growth at 37 degrees C in vitro. Viability of the dnaK null mutant was also greatly affected at low pH. In infection experiments performed with both mutants at the reduced temperature of 30 degrees C, the dnaK mutant of B suis survived but failed to multiply within U937 cells, whereas the wild-type strain and the dnaJ mutant multiplied normally. Complementation of the dnaK mutant with the cloned dnaK gene restored growth at 37 degrees C, increased resistance to acid pH, and increased intracellular multiplication [Ref6500:Köhler et al., 2002]. |
11854256
|
|
|
pmtA |
Brucella suis 1330 |
1167830
|
|
23502975
|
BR2127 |
AE014291 |
NP_699102 |
phospholipid N-methyltransferase |
Virulence factor |
MUTATION: The role of Phosphatidylcholine (PC) in Brucella abortus was examined by generating mutants in pcs (BApcs) and pmtA (BApmtA), which encode key enzymes of the two bacterial PC biosynthetic routes, the choline and methyl-transferase pathways. In rich medium, BApcs and the double mutant BApcspmtA but not BApmtA displayed reduced growth, increased phosphatidylethanolamine and no PC, showing that Pcs is essential for PC synthesis under these conditions. In minimal medium, the parental strain, BApcs and BApmtA showed reduced but significant amounts of PC suggesting that PmtA may also be functional Probing with phage Tb, antibiotics, polycations and serum demonstrated that all mutants had altered envelopes. In macrophages, BApcs and BApcspmtA showed reduced ability to evade fusion with lysosomes and establish a replication niche. In mice, BApcs showed attenuation only at early times after infection, BApmtA at later stages and BApcspmtA throughout. The results suggest that Pcs and PmtA have complementary roles in vivo related to nutrient availability and that PC and the membrane properties that depend on this typical eukaryotic phospholipid are essential for Brucella virulence [Ref6478:Conde-Alvarez et al., 2006]. |
16882035
|
|
|
mutM from Brucella suis 1330 |
Brucella suis 1330 |
1167886
|
|
23503030
|
BR2183 |
|
NP_699157.1 |
formamidopyrimidine-DNA glycosylase |
Virulence factor |
FUNCTION: Involved in base excision repair of DNA damaged by oxidation or by mutagenic agents. Acts as DNA glycosylase that recognizes and removes damaged bases. Has a preference for oxidized purines, such as 7,8-dihydro-8-oxoguanine (8-oxoG). Has AP (apurinic/apyrimidinic) lyase activity and introduces nicks in the DNA strand. Cleaves the DNA backbone by beta-delta elimination to generate a single-strand break at the site of the removed base with both 3'- and 5'-phosphates (By similarity)(Swiss-Prot: Q8FXR6).
CATALYTIC ACTIVITY: Hydrolysis of DNA containing ring-opened N(7)-methylguanine residues, releasing 2,6-diamino-4-hydroxy-5-(N-methyl)formamidopyrimidine(Swiss-Prot: Q8FXR6).
CATALYTIC ACTIVITY: The C-O-P bond 3' to the apurinic or apyrimidinic site in DNA is broken by a beta-elimination reaction, leaving a 3'-terminal unsaturated sugar and a product with a terminal 5'-phosphate(Swiss-Prot: Q8FXR6).
COFACTOR: Binds 1 zinc ion per subunit (By similarity)(Swiss-Prot: Q8FXR6).
SUBUNIT: Monomer (By similarity)(Swiss-Prot: Q8FXR6).
SIMILARITY: Belongs to the FPG family(Swiss-Prot: Q8FXR6).
SIMILARITY: Contains 1 FPG-type zinc finger(Swiss-Prot: Q8FXR6).
MUTATION: Attenuated in Differential fluorescence induction [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
hpt from Brucella melitensis bv. 1 str. 16M |
Brucella melitensis bv. 1 str. 16M |
1195794
|
|
17986366
|
BMEI0082 |
|
NP_539000.1 |
hypoxanthine-guanine phosphoribosyltransferase |
Virulence factor |
FUNCTIONAL GROUP: DNA/RNA metabolism, Synthesis [Ref6462:Delrue et al., 2004].
FUNCTION: Purines synthesis [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
lysA from Brucella melitensis bv. 1 str. 16M |
Brucella melitensis bv. 1 str. 16M |
1195796
|
|
17986368
|
BMEI0084 |
|
NP_539002.1 |
DIAMINOPIMELATE DECARBOXYLASE |
Virulence factor |
MUTATION: A study with miniTn5 mutants of B. suis constitutively expressing gfp indicates that B. suis lysA gene is required for intracellular multiplication in human macrophage THP-1 cells [Ref412:Kohler et al., 2002]. |
12438693
|
|
|
BMEI0085 |
Brucella |
1195797
|
|
17986369
|
BMEI0085 |
|
NP_539003.1 |
hypothetical protein |
Virulence factor |
FUNCTIONAL GROUP: Unkown function [Ref6462:Delrue et al., 2004].
FUNCTION: Brucella orphan gene [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Macrophages [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
omp19 from Brucella melitensis bv. 1 str. 16M |
Brucella melitensis bv. 1 str. 16M |
1195847
|
|
17986419
|
BMEI0135 |
|
NP_539053.1 |
OUTER MEMBRANE LIPOPROTEIN |
Virulence factor |
SUBCELLULAR LOCATION: Outer membrane; lipid-anchor(Swiss-Prot: P0A3P2).
MISCELLANEOUS: Elicits an immune response in humans, mice, sheep and goats infected with B.melitensis or B.abortus, but not in B.abortus-infected cattle(Swiss-Prot: P0A3P2).
SIMILARITY: Belongs to the rhizobiaceae omp19 lipoprotein family(Swiss-Prot: P0A3P2).
MUTATION: Omp19 is an immunoreactive outer membrane lipoprotein. Significantly fewer brucellae were recovered from the spleens of mice infected with the omp19 mutant than from those of mice infected with the parent strain at 4 and 8 weeks postinfection. The omp19 mutant exhibited an increase in sensitivity to the polycation polymyxin B and to sodium deoxycholate. These results indicate that inactivation of the omp19 gene alters the outer membrane properties of B abortus [Ref6473:Tibor et al., 2002]. |
12228280
|
|
|
rplS from Brucella melitensis bv. 1 str. 16M |
Brucella melitensis bv. 1 str. 16M |
1195868
|
|
17986440
|
BMEI0156 |
|
NP_539074.1 |
50S ribosomal protein L19 |
Virulence factor |
FUNCTION: This protein is located at the 30S-50S ribosomal subunit interface and may play a role in the structure and function of the aminoacyl-tRNA binding site (By similarity)(Swiss-Prot: P66079).
SIMILARITY: Belongs to the ribosomal protein L19P family(Swiss-Prot: P66079).
MUTATION: rplS is involved in traanslation. B. abortus rplS mutant by the mini-Tn5 disruption displays nutritional defects in vitro [Ref6485:Alcantara et al., 2004]. |
15271960
|
|
|
leuC from Brucella melitensis bv. 1 str. 16M |
Brucella melitensis bv. 1 str. 16M |
1195869
|
|
17986441
|
BMEI0157 |
|
NP_539075.1 |
isopropylmalate isomerase large subunit |
Virulence factor |
FUNCTION: Catalyzes the isomerization between 2-isopropylmalate and 3-isopropylmalate, via the formation of 2-isopropylmaleate(Swiss-Prot: Q8FYG9).
CATALYTIC ACTIVITY: (2R,3S)-3-isopropylmalate = (2S)-2-isopropylmaleate + H(2)O(Swiss-Prot: Q8FYG9).
CATALYTIC ACTIVITY: (2S)-2-isopropylmaleate + H(2)O = 3-hydroxy-4-methyl-3-carboxypentanoate(Swiss-Prot: Q8FYG9).
COFACTOR: Binds 1 4Fe-4S cluster per subunit (By similarity)(Swiss-Prot: Q8FYG9).
PATHWAY: Amino-acid biosynthesis; L-leucine biosynthesis; L-leucine from 3-methyl-2-oxobutanoate: step 2(Swiss-Prot: Q8FYG9).
SUBUNIT: Heterodimer of leuC and leuD (By similarity)(Swiss-Prot: Q8FYG9).
SIMILARITY: Belongs to the aconitase/IPM isomerase family. LeuC type 1 subfamily(Swiss-Prot: Q8FYG9).
MUTATION: A study with miniTn5 mutants of B. suis constitutively expressing gfp indicates that B. suis leuC gene is required for intracellular multiplication in human macrophage THP-1 cells [Ref412:Kohler et al., 2002]. |
12438693
|
|
|
gntR4 |
Brucella |
1195881
|
|
17986453
|
BMEI0169 |
|
NP_539087.1 |
TRANSCRIPTIONAL REGULATOR, GNTR FAMILY / AMINOTRANSFERASE CLASS-I |
Virulence factor |
FUNCTIONAL GROUP: gntR family [Ref6530:Haine et al., 2005].
MUTATION: Attenuated using plasmid-tagged mutagenesis method [Ref6530:Haine et al., 2005]. |
16113274
|
|
|
pstP |
Brucella melitensis bv. 1 str. 16M |
1195902
|
|
17986474
|
BMEI0190 |
NZ_GG703778 |
NP_539108 |
phosphoenolpyruvate-protein phosphotransferase PTSP |
Virulence factor |
FUNCTIONAL GROUP: "Classical virulence factors", Secretion of transport system, Flagella [Ref6462:Delrue et al., 2004].
FUNCTION: Phosphoenolypruvate phosphotransferase [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
purH from Brucella melitensis bv. 1 str. 16M |
Brucella melitensis bv. 1 str. 16M |
1195945
|
|
17986517
|
BMEI0233 |
|
NP_539151.1 |
bifunctional phosphoribosylaminoimidazolecarboxamide formyltransferase/IMP cyclohydrolase |
Virulence factor |
CATALYTIC ACTIVITY: 10-formyltetrahydrofolate + 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide = tetrahydrofolate + 5-formamido-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide(Swiss-Prot: P67540).
CATALYTIC ACTIVITY: IMP + H(2)O = 5-formamido-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide(Swiss-Prot: P67540).
PATHWAY: Nucleotide biosynthesis; IMP biosynthesis; 5-formamido-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide from 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide (10-formyl THF route): single step(Swiss-Prot: P67540).
PATHWAY: Nucleotide biosynthesis; IMP biosynthesis; IMP from 5-formamido-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide: single step [final step](Swiss-Prot: P67540).
PATHWAY: Context: Purine biosynthesis(Swiss-Prot: P67540).
DOMAIN: The IMP cyclohydrolase activity resides in the N-terminal region (By similarity)(Swiss-Prot: P67540).
SIMILARITY: Belongs to the purH family(Swiss-Prot: P67540).
MUTATION: B. abortus mutant with mini-Tn5-disrupted purH displays nutritional defects in vitro [Ref6485:Alcantara et al., 2004]. |
15271960
|
|
|
livH from Brucella melitensis bv. 1 str. 16M |
Brucella melitensis bv. 1 str. 16M |
1195970
|
|
17986542
|
BMEI0258 |
|
NP_539176.1 |
HIGH-AFFINITY BRANCHED-CHAIN AMINO ACID TRANSPORT SYSTEM PERMEASE PROTEIN LIVH |
Virulence factor |
FUNCTIONAL GROUP: a.a. metabolism, Transport [Ref6462:Delrue et al., 2004].
FUNCTION: Branched as transport system [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Differential fluorescence induction [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
pyc from Brucella melitensis bv. 1 str. 16M |
Brucella melitensis bv. 1 str. 16M |
1195978
|
|
17986550
|
BMEI0266 |
|
NP_539184.1 |
pyruvate carboxylase |
Virulence factor |
MUTATION: pyc is one B. suis gene identified by signature-tagged mutagenesis. It is essential for survival and mulitplication in macrophages [Ref6484:Foulongne et al., 2000]. |
10678941
|
|
|
mosC from Brucella melitensis bv. 1 str. 16M |
Brucella melitensis bv. 1 str. 16M |
1195979
|
|
17986551
|
BMEI0267 |
|
NP_539185.1 |
MEMBRANE PROTEIN MOSC |
Virulence factor |
FUNCTIONAL GROUP: a.a. metabolism, Transport [Ref6462:Delrue et al., 2004].
FUNCTION: Rhizopine transport [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Mice, but not in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
mgps |
Brucella melitensis bv. 1 str. 16M |
1195987
|
|
17986559
|
BMEI0275 |
AE008917 |
NP_539193 |
ATP-dependent DNA helicase |
Virulence factor |
FUNCTIONAL GROUP: DNA/RNA metabolism, Regulation [Ref6462:Delrue et al., 2004].
FUNCTION: RNA helicase family [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
purE from Brucella melitensis bv. 1 str. 16M |
Brucella melitensis bv. 1 str. 16M |
1196007
|
|
17986579
|
BMEI0296 |
|
NP_539213.1 |
PHOSPHORIBOSYLAMINOIMIDAZOLE CARBOXYLASE CATALYTIC SUBUNIT |
Virulence factor |
FUNCTION: This subunit can alone transform AIR to CAIR, but in association with purK, which possesses an ATPase activity, an enzyme complex is produced which is capable of converting AIR to CAIR efficiently under physiological condition (By similarity)(Swiss-Prot: Q8FYW3).
CATALYTIC ACTIVITY: 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxylate = 5-amino-1-(5-phospho-D-ribosyl)imidazole + CO(2)(Swiss-Prot: Q8FYW3).
PATHWAY: Nucleotide biosynthesis; IMP biosynthesis; 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide from N(2)-formyl-N(1)-(5-phospho-D-ribosyl)glycinamide: step 3(Swiss-Prot: Q8FYW3).
PATHWAY: Context: Purine biosynthesis(Swiss-Prot: Q8FYW3).
SUBUNIT: Homooctamer (By similarity)(Swiss-Prot: Q8FYW3).
SIMILARITY: Belongs to the AIR carboxylase family(Swiss-Prot: Q8FYW3).
MUTATION: Brucella abortus 2308 derivatives with mini-Tn5 insertions in purE, purL, and purD display significant attenuation in the BALBc mouse model. It confirms the importance of the purine biosynthesis pathways for the survival and replication of the brucellae in host macrophages [Ref6485:Alcantara et al., 2004]. The purE mutant has reduced survival in murine macrophages and reduced virulence in mice [Ref6485:Alcantara et al., 2004].
A purE gene deletion mutant (purE201) of B melitensis was constructed as a potentially useful vaccine for humans and animals. At necropsy, bacteria were present in mammary lymph nodes or spleen of 33 of goats given virulent 16M but in none of goats given the purE mutant. The purE mutation of B melitensis 16M was stable and that the vaccine could be differentiated from wild-type strains by hybridization, purine auxotrophy, and kanamycin resistance. Mice clear the identical purE mutant strain from their spleens in only 8 weeks but remain infected with B. melitensis 16M for at least 3 months [Ref6485:Alcantara et al., 2004]. |
15271960
|
|
|
gntR2 |
Brucella melitensis bv. 1 str. 16M |
1196016
|
|
17986588
|
BMEI0305 |
AE008917 |
NP_539222 |
DeoR family transcriptional regulator |
Virulence factor |
FUNCTIONAL GROUP: gntR family [Ref6530:Haine et al., 2005].
MUTATION: Attenuated in mice [Ref6530:Haine et al., 2005]. |
16113274
|
|
|
gntR17 |
Brucella melitensis bv. 1 str. 16M |
1196031
|
|
17986603
|
BMEI0320 |
AE008917 |
NP_539237 |
GntR family transcriptional regulator |
Virulence factor |
FUNCTIONAL GROUP: gntR family [Ref6530:Haine et al., 2005].
MUTATION: Attenuated in mice [Ref6530:Haine et al., 2005]. |
16113274
|
|
|
ansC from Brucella melitensis bv. 1 str. 16M |
Brucella melitensis bv. 1 str. 16M |
1196068
|
|
17986640
|
BMEI0357 |
|
NP_539274.1 |
TRANSCRIPTIONAL REGULATORY PROTEIN, ASNC FAMILY |
Virulence factor |
FUNCTIONAL GROUP: "Classical virulence factors", Secretion of transport system, Flagella [Ref6462:Delrue et al., 2004].
FUNCTION: Transcriptional regulator [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
dut from Brucella melitensis bv. 1 str. 16M |
Brucella melitensis bv. 1 str. 16M |
1196069
|
|
17986641
|
BMEI0358 |
|
NP_539275.1 |
deoxyuridine 5'-triphosphate nucleotidohydrolase |
Virulence factor |
FUNCTION: This enzyme is involved in nucleotide metabolism: it produces dUMP, the immediate precursor of thymidine nucleotides and it decreases the intracellular concentration of dUTP so that uracil cannot be incorporated into DNA (By similarity)(Swiss-Prot: P64005).
CATALYTIC ACTIVITY: dUTP + H(2)O = dUMP + diphosphate(Swiss-Prot: P64005).
PATHWAY: De novo synthesis of thymidylate(Swiss-Prot: P64005).
SIMILARITY: Belongs toMUTATION: A study with miniTn5 mutants of B. suis constitutively expressing gfp indicates that B. suis dut gene is required for intracellular multiplication in human macrophage THP-1 cells [Ref412:Kohler et al., 2002]. the dUTPase family(Swiss-Prot: P64005). |
12438693
|
|
|
macA from Brucella melitensis bv. 1 str. 16M |
Brucella melitensis bv. 1 str. 16M |
1196070
|
|
17986642
|
BMEI0359 |
|
NP_539276.1 |
periplasmic component of efflux system |
Virulence factor |
FUNCTIONAL GROUP: "Classical virulence factors", Secretion of transport system, Transpter [Ref6462:Delrue et al., 2004].
FUNCTION: Macrolide efflux [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
alkA from Brucella melitensis bv. 1 str. 16M |
Brucella melitensis bv. 1 str. 16M |
1196093
|
|
17986665
|
BMEI0382 |
|
NP_539299.1 |
DNA-3-METHYLADENINE GLYCOSIDASE |
Virulence factor |
FUNCTIONAL GROUP: DNA/RNA metabolism, Repair [Ref6462:Delrue et al., 2004].
FUNCTION: HhH-GPD superfamily base excision DNA repair [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
dsbB from Brucella melitensis bv. 1 str. 16M |
Brucella melitensis bv. 1 str. 16M |
1196095
|
|
17986667
|
BMEI0384 |
|
NP_539301.1 |
DISULFIDE BOND FORMATION PROTEIN B |
Virulence factor |
FUNCTIONAL GROUP: Oxidoreduction [Ref6462:Delrue et al., 2004].
FUNCTION: Disulfide bond formation protein [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Mice, Macrophages [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
arsR6 |
Brucella melitensis bv. 1 str. 16M |
1196141
|
|
17986713
|
BMEI0430 |
AE008917 |
NP_539347 |
nodulation protein NOLR |
Virulence factor |
FUNCTIONAL GROUP: ArsR family [Ref6530:Haine et al., 2005].
MUTATION: Attenuated in mice [Ref6530:Haine et al., 2005]. |
16113274
|
|
|
dppA from Brucella melitensis bv. 1 str. 16M |
Brucella melitensis bv. 1 str. 16M |
1196144
|
|
17986716
|
BMEI0433 |
|
NP_539350.1 |
PERIPLASMIC DIPEPTIDE TRANSPORT PROTEIN PRECURSOR |
Virulence factor |
FUNCTIONAL GROUP: a.a. metabolism, Transport [Ref6462:Delrue et al., 2004].
FUNCTION: Dipeptide uptake [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
leuA from Brucella melitensis bv. 1 str. 16M |
Brucella melitensis bv. 1 str. 16M |
1196162
|
|
17986734
|
BMEI0451 |
|
NP_539368.1 |
2-isopropylmalate synthase |
Virulence factor |
FUNCTION: Catalyzes the condensation of the acetyl group of acetyl-CoA with 3-methyl-2-oxobutanoate (2-oxoisovalerate) to form 3-carboxy-3-hydroxy-4-methylpentanoate (2-isopropylmalate)(Swiss-Prot: Q8FZC4).
CATALYTIC ACTIVITY: Acetyl-CoA + 3-methyl-2-oxobutanoate + H(2)O = (2S)-2-isopropylmalate + CoA(Swiss-Prot: Q8FZC4).
PATHWAY: Amino-acid biosynthesis; L-leucine biosynthesis; L-leucine from 3-methyl-2-oxobutanoate: step 1(Swiss-Prot: Q8FZC4).
SUBUNIT: Homotetramer (By similarity)(Swiss-Prot: Q8FZC4).
SIMILARITY: Belongs to the alpha-IPM synthetase/homocitrate synthase family. LeuA type 2 subfamily(Swiss-Prot: Q8FZC4).
MUTATION: leuA is a B. suis gene identified by signature-tagged mutagenesis. It is attenuated inside THP1 macrophage cell line. |
|
|
|
BMEI0455 |
Brucella |
1196166
|
|
17986738
|
BMEI0455 |
|
NP_539372.1 |
GLUTATHIONE S-TRANSFERASE |
Virulence factor |
FUNCTIONAL GROUP: Unkown function [Ref6462:Delrue et al., 2004].
FUNCTION: Glutathione S-transferase, C-terminal domain [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
pth from Brucella melitensis bv. 1 str. 16M |
Brucella melitensis bv. 1 str. 16M |
1196191
|
|
17986763
|
BMEI0480 |
|
NP_539397.1 |
peptidyl-tRNA hydrolase |
Virulence factor |
FUNCTION: The natural substrate for this enzyme may be peptidyl-tRNAs which drop off the ribosome during protein synthesis (By similarity)(Swiss-Prot: P65864).
CATALYTIC ACTIVITY: N-substituted aminoacyl-tRNA + H(2)O = N-substituted amino acid + tRNA(Swiss-Prot: P65864).
SUBUNIT: Monomer (By similarity)(Swiss-Prot: P65864).
SUBCELLULAR LOCATION: Cytoplasm (By similarity)(Swiss-Prot: P65864).
SIMILARITY: Belongs to the PTH family(Swiss-Prot: P65864).
MUTATION: pth encodes for a peptidyl tRNA hydrolase. Transposon insertion in pth has a polar effect on dugA expression and that the pth/dugA mutant is deficient in iron assimilation because of altered expression of the dugA gene. Only minor difference in intracellular growth in bovine macrophages and HeLa cells between the pth/dugA mutant and wild-type strains was observed [Ref6498:Danese et al., 2004]. |
15385478
|
|
|
lpsB |
Brucella melitensis bv. 1 str. 16M |
1196220
|
|
17986792
|
BMEI0509 |
|
NP_539426.1 |
LIPOPOLYSACCHARIDE CORE BIOSYNTHESIS MANNOSYLTRANSFERASE LPCC |
Virulence factor |
FUNCTIONAL GROUP: "Classical virulence factors", Envelope molecules, Lipopolysaccharide [Ref6462:Delrue et al., 2004].
FUNCTION: Core synthesis [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Macrophages [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
trkH |
Brucella melitensis bv. 1 str. 16M |
1196223
|
|
17986795
|
BMEI0512 |
NZ_GG703780 |
NP_539429 |
thioredoxin reductase |
Virulence factor |
FUNCTIONAL GROUP: Oxidoreduction [Ref6462:Delrue et al., 2004].
FUNCTION: Thioredoxin reductase [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Differential fluorescence induction [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
lysR from Brucella melitensis bv. 1 str. 16M |
Brucella melitensis bv. 1 str. 16M |
1196224
|
|
17986796
|
BMEI0513 |
|
NP_539430.1 |
TRANSCRIPTIONAL REGULATORY PROTEIN, LYSR FAMILY |
Virulence factor |
FUNCTIONAL GROUP: "Classical virulence factors", Secretion of transport system, Flagella [Ref6462:Delrue et al., 2004].
FUNCTION: Transcriptional regulator [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
aspC from Brucella melitensis bv. 1 str. 16M |
Brucella melitensis bv. 1 str. 16M |
1196227
|
|
17986799
|
BMEI0516 |
|
NP_539433.1 |
aspartate aminotransferase |
Virulence factor |
MUTATION: aspC encodes for an aminotransferase. B.abortus aspC mutant obtained from randomized miniTn5Km2 transposon mutagenesis showed decreased intracellular survival inside HeLa cells. So B. abortus aspC gene is essential for HeLa cell intracellular growth [Ref6469:Kim et al., 2003]. |
12761078
|
|
|
carAB |
Brucella melitensis bv. 1 str. 16M |
1196237
|
|
161511156
|
BMEI0526 |
NZ_GG703780 |
NP_539443 |
carbamoyl phosphate synthase small subunit |
Virulence factor |
FUNCTIONAL GROUP: a.a. metabolism, Synthesis [Ref6462:Delrue et al., 2004].
FUNCTION: Clut. and pyr. Syntheis [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Macrophages [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
pncA from Brucella melitensis bv. 1 str. 16M |
Brucella melitensis bv. 1 str. 16M |
1196256
|
|
17986828
|
BMEI0545 |
|
NP_539462.1 |
INTEGRAL MEMBRANE PROTEIN |
Virulence factor |
MUTATION: Brucella abortus pnc mutant via mini-Tn5Km2 transposon mutagenesis has intracellular growth defect inside HeLa cells [Ref6469:Kim et al., 2003]. Nicotinamidasepyrazinamidase mutant (pncA mutant) of Brucella abortus failed to replicate in HeLa cells, and showed a lower rate of intracellular replication than that of wild-type strain in macrophages [Ref6468:Kim et al., 2004]. The pncA mutant was not co-localizing with either late endosomes or lysosomes. The pncA mutant showed a 1.5-log reduction of the number of bacteria isolated from mouse spleens after 10 weeks [Ref6468:Kim et al., 2004]. It indicates that the mutant has reduced virulence in mice. |
12761078
15135535
|
|
|
bicA |
Brucella melitensis bv. 1 str. 16M |
1196316
|
|
17986888
|
BMEI0605 |
AE008917 |
NP_539522 |
bicyclomycin resistance protein |
Virulence factor |
FUNCTIONAL GROUP: "Classical virulence factors", Secretion of transport system, Transpter [Ref6462:Delrue et al., 2004].
FUNCTION: Macrolide efflux [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Macrophages [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
serB from Brucella melitensis bv. 1 str. 16M |
Brucella melitensis bv. 1 str. 16M |
1196326
|
|
17986898
|
BMEI0615 |
|
NP_539532.1 |
PHOSPHOSERINE PHOSPHATASE |
Virulence factor |
MUTATION: A study with miniTn5 mutants of B. suis constitutively expressing gfp indicates that B. suis serB gene is required for intracellular multiplication in human macrophage THP-1 cells [Ref412:Kohler et al., 2002]. |
12438693
|
|
|
miaA from Brucella melitensis bv. 1 str. 16M |
Brucella melitensis bv. 1 str. 16M |
1196327
|
|
17986899
|
BMEI0616 |
|
NP_539533.1 |
tRNA delta(2)-isopentenylpyrophosphate transferase |
Virulence factor |
FUNCTION: Catalyzes the first step in the biosynthesis of 2-methylthio-N6-(delta(2)-isopentenyl)-adenosine (MS[2]I[6]A) adjacent to the anticodon of several tRNA species (By similarity)(Swiss-Prot: Q8CY40).
CATALYTIC ACTIVITY: Isopentenyl diphosphate + tRNA = diphosphate + tRNA containing 6-isopentenyladenosine(Swiss-Prot: Q8CY40).
SIMILARITY: Belongs to the IPP transferase family(Swiss-Prot: Q8CY40).
MUTATION: A study with miniTn5 mutants of B. suis constitutively expressing gfp indicates that B. suis miaA gene is required for intracellular multiplication in human macrophage THP-1 cells [Ref412:Kohler et al., 2002]. |
12438693
|
|
|
ilvI |
Brucella melitensis bv. 1 str. 16M |
1196328
|
|
17986900
|
BMEI0617 |
HD006899 |
NP_539534 |
acetolactate synthase 3 catalytic subunit |
Virulence factor |
FUNCTIONAL GROUP: a.a. metabolism, Synthesis [Ref6462:Delrue et al., 2004].
FUNCTION: Val. Leu., Isoleu. Synthesis [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
ilvCv from Brucella melitensis bv. 1 str. 16M |
Brucella melitensis bv. 1 str. 16M |
1196335
|
|
17986907
|
BMEI0624 |
|
NP_539541.1 |
ketol-acid reductoisomerase |
Virulence factor |
CATALYTIC ACTIVITY: (R)-2,3-dihydroxy-3-methylbutanoate + NADP(+) = (S)-2-hydroxy-2-methyl-3-oxobutanoate + NADPH(Swiss-Prot: Q8FZU1).
CATALYTIC ACTIVITY: (2R,3R)-2,3-dihydroxy-3-methylpentanoate + NADP(+) = (S)-2-hydroxy-2-ethyl-3-oxobutanoate + NADPH(Swiss-Prot: Q8FZU1).
PATHWAY: Amino-acid biosynthesis; L-isoleucine biosynthesis; L-isoleucine from 2-oxobutanoate: step 2(Swiss-Prot: Q8FZU1).
PATHWAY: Amino-acid biosynthesis; L-valine biosynthesis; L-valine from pyruvate: step 2(Swiss-Prot: Q8FZU1).
SIMILARITY: Belongs to the ketol-acid reductoisomerase family(Swiss-Prot: Q8FZU1).
MUTATION: ilvC is one of the 37 mutants with virulene defect, screened out from the signature- tagged miniTn5 library [Ref6480:Lestrate et al., 2003]. |
14638795
|
|
|
aspB from Brucella suis 1330 |
Brucella suis 1330 |
1196337
|
|
17986909
|
BMEI0626 |
|
NP_539543.1 |
TRANSCRIPTIONAL REGULATOR, GNTR FAMILY / MULTIPLE SUBSTRATE AMINOTRANSFERASE |
Virulence factor |
FUNCTIONAL GROUP: a.a. metabolism, Unkown [Ref6462:Delrue et al., 2004].
FUNCTION: Aminotransferase [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Macrophages [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
BMEI0671 |
Brucella |
1196382
|
|
17986954
|
BMEI0671 |
|
NP_539588.1 |
INTEGRAL MEMBRANE PROTEIN / HEMOLYSIN |
Virulence factor |
FUNCTIONAL GROUP: Unkown function [Ref6462:Delrue et al., 2004].
FUNCTION: Terc dome (efflux) [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Macrophages [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
cobB from Brucella melitensis bv. 1 str. 16M |
Brucella melitensis bv. 1 str. 16M |
1196416
|
|
17986988
|
BMEI0705 |
|
NP_539622.1 |
cobyrinic acid a,c-diamide synthase |
Virulence factor |
FUNCTION: Responsible for the amidation of carboxylic groups at position A and C of either cobyrinic acid or hydrogenobrynic acid. NH(2) groups are provided by glutamine, and one molecule of ATP is hydrogenolyzed for each amidation (By similarity)(Swiss-Prot: Q8G020).
PATHWAY: Cobalamin biosynthesis(Swiss-Prot: Q8G020).
SIMILARITY: Belongs to the cobB/cobQ family. CobB subfamily(Swiss-Prot: Q8G020).
MUTATION: 1,152 signature-tagged mutagenesis mutants of Brucella melitensis 16M were screened in a mouse model of infection. 36 of them to be attenuated in vivo. cobB is one of them [Ref6480:Lestrate et al., 2003]. |
14638795
|
|
|
thrA |
Brucella melitensis bv. 1 str. 16M |
1196436
|
|
17987008
|
BMEI0725 |
AE008917 |
NP_539642 |
homoserine dehydrogenase |
Virulence factor |
FUNCTIONAL GROUP: a.a. metabolism, Synthesis [Ref6462:Delrue et al., 2004].
FUNCTION: Lys. synthesis [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Macrophages [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
gloA from Brucella melitensis bv. 1 str. 16M |
Brucella melitensis bv. 1 str. 16M |
1196441
|
|
17987013
|
BMEI0730 |
|
NP_539647.1 |
LACTOYLGLUTATHIONE LYASE |
Virulence factor |
FUNCTIONAL GROUP: a.a. metabolism, Unkown [Ref6462:Delrue et al., 2004].
FUNCTION: Lactoylglutathione lyase (pyruvate metabolism) [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Differential fluorescence induction [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
rpoA from Brucella melitensis bv. 1 str. 16M |
Brucella melitensis bv. 1 str. 16M |
1196492
|
|
17987064
|
BMEI0781 |
|
NP_539698.1 |
DNA-directed RNA polymerase subunit alpha |
Virulence factor |
FUNCTION: DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates(Swiss-Prot: Q8G094).
CATALYTIC ACTIVITY: Nucleoside triphosphate + RNA(n) = diphosphate + RNA(n+1)(Swiss-Prot: Q8G094).
SUBUNIT: Homodimer. The RNAP catalytic core consists of 2 alpha, 1 beta, 1 beta' and 1 omega subunit. When a sigma factor is associated with the core the holoenzyme is formed, which can initiate transcription (By similarity)(Swiss-Prot: Q8G094).
DOMAIN: The N-terminal domain is essential for RNAP assembly and basal transcription, whereas the C-terminal domain is involved in interaction with transcriptional regulators and with upstream promoter elements (By similarity)(Swiss-Prot: Q8G094).
SIMILARITY: Belongs to the RNA polymerase alpha chain family(Swiss-Prot: Q8G094).
MUTATION: The rpoA gene codes for the essential alpha-subunit of the RNA polymerase. B. melitensis rpoA mutant was found by signature-tagged mutagenesis from a mouse infection model. This disruption leaves a partially functional protein, impaired for the activation of virB transcription, as demonstrated by the absence of induction of the virB promoter in the Tn5::rpoA background. RpoA is involved in virB regulation in vitro. The mutant (Tn5::rpoA) was more resistant to oxidative stress [Ref6480:Lestrate et al., 2003]. |
14638795
|
|
|
recA from Brucella melitensis bv. 1 str. 16M |
Brucella melitensis bv. 1 str. 16M |
1196498
|
|
17987070
|
BMEI0787 |
|
NP_539704.1 |
recombinase A |
Virulence factor |
FUNCTION: Can catalyze the hydrolysis of ATP in the presence of single-stranded DNA, the ATP-dependent uptake of single-stranded DNA by duplex DNA, and the ATP-dependent hybridization of homologous single-stranded DNAs. It interacts with lexA causing its activation and leading to its autocatalytic cleavage (By similarity)(Swiss-Prot: P65976).
SUBCELLULAR LOCATION: Cytoplasm (By similarity)(Swiss-Prot: P65976).
SIMILARITY: Belongs to the recA family(Swiss-Prot: P65976).
MUTATION: The RecA mutant was more sensitive than the parental strain to killing by MMS. When administered intraperitoneally to BALBc mice, numbers of bacteria per spleen were consistently lower in animals infected with the RecA mutant than with the parental strain. However, both the RecA mutant and parental strain persisted in mice through 100 days post-infection. These results indicate that RecA is not crucial for persistence of B abortus in mice [Ref6531:Tatum et al., 1993].
The B abortus RecA mutant was virulent in mice, but its course of infection in mice differed from that of the parental strain. The infectious cycle of the parental strain in the mouse model was biphasic. During the rst week, there was an initial rise in cfu of B abortus 2308 in the spleen followed by a decrease during the second week. This phase was followed by a second phase in which B abortus S2308 persisted and slowly increased in numbers in the spleen . Though fewer RecA mutants were found in the spleens of mice infected intraperitoneally in the early stages of the infection and no large initial rise was seen, the same numbers were found as the parental strain 100 days post -infection. This suggests that collectively, different loci are involved to varying extents in the initial infection and the persistence phase [Ref6531:Tatum et al., 1993].
|
8321120
|
|
|
uppS from Brucella melitensis bv. 1 str. 16M |
Brucella melitensis bv. 1 str. 16M |
1196538
|
|
17987110
|
BMEI0827 |
|
NP_539744.1 |
UNDECAPRENYL PYROPHOSPHATE SYNTHETASE |
Virulence factor |
FUNCTION: Generates undecaprenyl pyrophosphate (UPP) from isopentenyl pyrophosphate (IPP). UPP is the precursor of glycosyl carrier lipid in the biosynthesis of bacterial cell wall polysaccharide components such as peptidoglycan and lipopolysaccharide (By similarity)(Swiss-Prot: Q8G0D9).
CATALYTIC ACTIVITY: Di-trans,poly-cis-decaprenyl diphosphate + isopentenyl diphosphate = diphosphate + di-trans,poly-cis-undecaprenyl diphosphate(Swiss-Prot: Q8G0D9).
COFACTOR: Magnesium (By similarity)(Swiss-Prot: Q8G0D9).
SUBUNIT: Homodimer (By similarity)(Swiss-Prot: Q8G0D9).
SIMILARITY: Belongs to the UPP synthetase family(Swiss-Prot: Q8G0D9).
MUTATION: A study with miniTn5 mutants of B. suis constitutively expressing gfp indicates that B. suis uppS gene is required for intracellular multiplication in human macrophage THP-1 cells [Ref412:Kohler et al., 2002]. |
12438693
|
|
|
ppiD from Brucella melitensis bv. 1 str. 16M |
Brucella melitensis bv. 1 str. 16M |
1196556
|
|
17987128
|
BMEI0845 |
|
NP_539762.1 |
PEPTIDYL-PROLYL CIS-TRANS ISOMERASE D |
Virulence factor |
FUNCTIONAL GROUP: Stress proteins/Chaperones [Ref6462:Delrue et al., 2004].
FUNCTION: Rotamase D [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
ntrY from Brucella melitensis bv. 1 str. 16M |
Brucella melitensis bv. 1 str. 16M |
1196578
|
|
17987150
|
BMEI0867 |
|
NP_539784.1 |
NITROGEN REGULATION PROTEIN NTRY |
Virulence factor |
MUTATION: The NtrY protein is a sensor of an ntr-related regulon which may be part of the glnALG operon. This mutant has a weakly attenuated phenotype (reduction of 1.2 log units versus the wild type at 48 h postinfection) which could be explained by a pleiotropic effect on the ntr regulon, since the ntrC mutant did not show such a phenotype [Ref6484:Foulongne et al., 2000]. |
10678941
|
|
|
hfq from Brucella melitensis bv. 1 str. 16M |
Brucella melitensis bv. 1 str. 16M |
1196583
|
|
17987155
|
BMEI0872 |
|
NP_539789.1 |
RNA-binding protein Hfq |
Virulence factor |
FUNCTION: RNA-binding protein that stimulates the elongation of poly(A) tails (By similarity)(Swiss-Prot: P0A3G8).
SIMILARITY: Belongs to the hfq family(Swiss-Prot: P0A3G8).
MUTATION: hfq encodes for the RNA binding protein host factor I (HF-I). The hfq knock out strain has been showed a reduced growth rate and is unable to utilize glucose as a sole carbon source[Ref6495:Sonnleitner et al., 2003].
hfq is required for the efficient translation of the stationary-phase sigma factor RpoS in many bacteria, and a Brucella abortus hfq mutant displays a phenotype in vitro, which suggests that it has a generalized defect in stationary-phase physiology. The inability of the B. abortus hfq mutant to survive and replicate in a wild-type manner in cultured murine macrophages, and the profound attenuation displayed by this strain and its B melitensis counterpart in experimentally infected animals indicate that stationary -phase physiology plays an essential role in the capacity of the brucellae to establish and maintain long-term intracellular residence in host macrophages [Ref6532:Roop et al., 2003].
In contrast to B abortus 2308, the isogenic hfq and bacA mutants remained in acidic, LAMP-1 phagosomes and failed to initiate intracellular replication [Ref6532:Roop et al., 2003].
A hfq mutant of B abortus was eliminated from mouse spleens more rapidly than the wild type [Ref6532:Roop et al., 2003]. |
14521880
12730323
|
|
|
lon from Brucella melitensis bv. 1 str. 16M |
Brucella melitensis bv. 1 str. 16M |
1196587
|
|
17987159
|
BMEI0876 |
|
NP_539793.1 |
ATP-DEPENDENT PROTEASE LA |
Virulence factor |
FUNCTION: Degrades short-lived regulatory and abnormal proteins in presence of ATP. Hydrolyzes two ATPs for each peptide bond cleaved in the protein substrate (By similarity)(Swiss-Prot: Q8G0I7).
CATALYTIC ACTIVITY: Hydrolysis of proteins in presence of ATP(Swiss-Prot: Q8G0I7).
SUBUNIT: Homotetramer (By similarity)(Swiss-Prot: Q8G0I7).
SUBCELLULAR LOCATION: Cytoplasm (By similarity)(Swiss-Prot: Q8G0I7).
SIMILARITY: Belongs to the peptidase S16 family(Swiss-Prot: Q8G0I7).
SIMILARITY: Contains 1 Lon domain(Swiss-Prot: Q8G0I7).
MUTATION: In contrast to the parent strain, the Brucella abortus lon mutant, was impaired in its capacity to form isolated colonies on solid medium at 41 degrees C and displayed an increased sensitivity to killing by puromycin and H2O2. Brucella abortus Lon homologue functions as a stress response protease that is required for wild-type virulence during the initial stages of infection in the mouse model, but is not essential for the establishment and maintenance of chronic infection in this host [Ref6494:Robertson et al., 2000].
Both single lon or clpA mutations had comparable effects on growth inhibition, suggesting that the concerned proteases Lon and ClpAP both degrade a number of specific proteins, but are also both involved in general degradation of abnormal proteins. Compared to the single mutants, the double mutant lon clpA was highly sensitive to canavanine. One possible explanation for this observation is that both proteases can substitute for each other to a large extent during bacterial growth. Hence, simultaneous inactivation or decrease in activation of both proteases, either by direct mutation or by elimination of the regulatory component ClpA, strongly increased growth inhibition [Ref6494:Robertson et al., 2000]. |
10672180
|
|
|
uvrA from Brucella melitensis bv. 1 str. 16M |
Brucella melitensis bv. 1 str. 16M |
1196589
|
|
17987161
|
BMEI0878 |
|
NP_539795.1 |
excinuclease ABC subunit A |
Virulence factor |
FUNCTION: The UvrABC repair system catalyzes the recognition and processing of DNA lesions. UvrA is an ATPase and a DNA-binding protein. A damage recognition complex composed of 2 uvrA and 2 uvrB subunits scans DNA for abnormalities. When the presence of a lesion has been verified by uvrB, the uvrA molecules dissociate (By similarity)(Swiss-Prot: Q8G0I9).
SUBUNIT: Forms a heterotetramer with uvrB during the search for lesions (By similarity)(Swiss-Prot: Q8G0I9).
SUBCELLULAR LOCATION: Cytoplasm (By similarity)(Swiss-Prot: Q8G0I9).
SIMILARITY: Belongs to the ABC transporter family. UvrA subfamily(Swiss-Prot: Q8G0I9).
SIMILARITY: Contains 2 ABC transporter domains(Swiss-Prot: Q8G0I9).
MUTATION: B. abortus urvA and recA mutants exhibited greater sensitivity than the wild-type strain. Mutant strains carrying inactivated uvrA genes are typically less sensitive than recA mutants because there is only the loss of the nucleotide excision repair system, just one subset of the larger repair networks. However, it was found that the recA mutant conferred only a modest sensitivity to UV, substantially less sensitive than the uvrA mutant. High basal recA expression was observed in the uvrA repair mutant. The B abortus recA mutant exhibited a nearly fourfold decline in survival to murine peritoneal macrophages but nominal sensitivity for the uvrA and radA repair mutants [Ref6493:Roux et al., 2006]. |
16816190
|
|
|
gntR5 |
Brucella |
1196592
|
|
17987164
|
BMEI0881 |
|
NP_539798.1 |
TRANSCRIPTIONAL REGULATOR, GNTR FAMILY |
Virulence factor |
FUNCTIONAL GROUP: gntR family [Ref6530:Haine et al., 2005].
MUTATION: Attenuated using plasmid-tagged mutagenesis method [Ref6530:Haine et al., 2005]. |
16113274
|
|
|
caiB from Brucella melitensis bv. 1 str. 16M |
Brucella melitensis bv. 1 str. 16M |
1196609
|
|
17987181
|
BMEI0898 |
|
NP_539815.1 |
Predicted acyl-CoA transferase/carnitine dehydratase |
Virulence factor |
FUNCTIONAL GROUP: Oxidoreduction [Ref6462:Delrue et al., 2004].
FUNCTION: CAIB/BAIF family [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Macrophages [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
cysK from Brucella melitensis bv. 1 str. 16M |
Brucella melitensis bv. 1 str. 16M |
1196644
|
|
17987216
|
BMEI0933 |
|
NP_539850.1 |
cysteine synthase A |
Virulence factor |
FUNCTIONAL GROUP: a.a. metabolism, Synthesis [Ref6462:Delrue et al., 2004].
FUNCTION: Cys. synthesis [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
glnA from Brucella melitensis bv. 1 str. 16M |
Brucella melitensis bv. 1 str. 16M |
1196690
|
|
17987262
|
BMEI0979 |
|
NP_539896.1 |
GLUTAMINE SYNTHETASE |
Virulence factor |
MUTATION: A study with miniTn5 mutants of B. suis constitutively expressing gfp indicates that B. suis glnA gene is required for intracellular multiplication in human macrophage THP-1 cells [Ref412:Kohler et al., 2002]. |
12438693
|
|
|
wbdA from Brucella melitensis bv. 1 str. 16M |
Brucella melitensis bv. 1 str. 16M |
1196708
|
|
17987280
|
BMEI0997 |
|
NP_539914.1 |
MANNOSYLTRANSFERASE |
Virulence factor |
FUNCTIONAL GROUP: "Classical virulence factors", Envelope molecules, Lipopolysaccharide [Ref6462:Delrue et al., 2004].
FUNCTION: O-chain biosynthesis [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Macrophages [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
caiB from Brucella melitensis bv. 1 str. 16M |
Brucella melitensis bv. 1 str. 16M |
1196730
|
|
17987302
|
BMEI1019 |
|
NP_539936.1 |
molybdenum cofactor biosynthesis protein A |
Virulence factor |
FUNCTIONAL GROUP: Oxidoreduction [Ref6462:Delrue et al., 2004].
FUNCTION: CAIB/BAIF family [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Macrophages [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
dsbA from Brucella melitensis bv. 1 str. 16M |
Brucella melitensis bv. 1 str. 16M |
1196751
|
|
17987323
|
BMEI1040 |
|
NP_539957.1 |
ABC TRANSPORTER ATP-BINDING PROTEIN |
Virulence factor |
FUNCTIONAL GROUP: Oxidoreduction [Ref6462:Delrue et al., 2004].
FUNCTION: Disulfide bond formation protein [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
nifS from Brucella melitensis bv. 1 str. 16M |
Brucella melitensis bv. 1 str. 16M |
1196754
|
|
17987326
|
BMEI1043 |
|
NP_539960.1 |
NIFS PROTEIN |
Virulence factor |
FUNCTIONAL GROUP: Nitrogen metabolism [Ref6462:Delrue et al., 2004].
FUNCTION: nitrogenase cofactor synthesis protein nifS [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Macrophages [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
amiC from Brucella melitensis bv. 1 str. 16M |
Brucella melitensis bv. 1 str. 16M |
1196767
|
|
17987339
|
BMEI1056 |
AE008917 |
NP_539973 |
N-acetylmuramoyl-L-alanine amidase |
Virulence factor |
FUNCTIONAL GROUP: "Classical virulence factors", Envelope molecules, peptidoglycan [Ref6462:Delrue et al., 2004].
FUNCTION: Cell-wall hydrolysis [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
dsbA from Brucella melitensis bv. 1 str. 16M |
Brucella melitensis bv. 1 str. 16M |
1196771
|
|
17987343
|
BMEI1060 |
|
NP_539977.1 |
OUTER MEMBRANE PROTEIN |
Virulence factor |
FUNCTIONAL GROUP: Oxidoreduction [Ref6462:Delrue et al., 2004].
FUNCTION: Disulfide bond formation protein [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
tig from Brucella melitensis bv. 1 str. 16M |
Brucella melitensis bv. 1 str. 16M |
1196780
|
|
17987352
|
BMEI1069 |
|
NP_539986.1 |
trigger factor |
Virulence factor |
FUNCTION: Involved in protein export. Acts as a chaperone by maintaining the newly synthesized protein in an open conformation (By similarity)(Swiss-Prot: Q8G129).
SIMILARITY: Belongs to the FKBP-type PPIase family. Tig subfamily(Swiss-Prot: Q8G129).
SIMILARITY: Contains 1 PPIase FKBP-type domain(Swiss-Prot: Q8G129).
MUTATION: tig encodes for Trigger factor that helps protein folding and secretion. It is one of the attenuated Signature-Tagged Mutagenesis mutants of Brucella melitensis identified during the acute phase of infection in mice [Ref6480:Lestrate et al., 2003]. |
14638795
|
|
|
artI from Brucella melitensis bv. 1 str. 16M |
Brucella melitensis bv. 1 str. 16M |
1196815
|
|
17987387
|
BMEI1104 |
|
NP_540021.1 |
ARGININE/ORNITHINE-BINDING PERIPLASMIC PROTEIN PRECURSOR |
Virulence factor |
FUNCTIONAL GROUP: a.a. metabolism, Transport [Ref6462:Delrue et al., 2004].
FUNCTION: Arginine transport system [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Differential fluorescence induction [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
cbbE |
Brucella melitensis bv. 1 str. 16M |
1196827
|
|
17987399
|
BMEI1116 |
AE008917 |
NP_540033 |
ribulose-phosphate 3-epimerase |
Virulence factor |
FUNCTIONAL GROUP: a.a. metabolism, Unkown [Ref6462:Delrue et al., 2004].
FUNCTION: Ribulose-phosphate 3-epimerase [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
purL from Brucella melitensis bv. 1 str. 16M |
Brucella melitensis bv. 1 str. 16M |
1196838
|
|
17987410
|
BMEI1127 |
|
NP_540044.1 |
phosphoribosylformylglycinamidine synthase II |
Virulence factor |
CATALYTIC ACTIVITY: ATP + N(2)-formyl-N(1)-(5-phospho-D-ribosyl)glycinamide + L-glutamine + H(2)O = ADP + phosphate + 2-(formamido)-N(1)-(5-phospho-D-ribosyl)acetamidine + L-glutamate(Swiss-Prot: Q8G183).
PATHWAY: Nucleotide biosynthesis; IMP biosynthesis; 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide from N(2)-formyl-N(1)-(5-phospho-D-ribosyl)glycinamide: step 1(Swiss-Prot: Q8G183).
PATHWAY: Context: Purine biosynthesis(Swiss-Prot: Q8G183).
SUBUNIT: Heterodimer of two subunits, purQ and purL(Swiss-Prot: Q8G183).
SUBCELLULAR LOCATION: Cytoplasm (By similarity)(Swiss-Prot: Q8G183).
SIMILARITY: Belongs to the FGAMS family(Swiss-Prot: Q8G183).
MUTATION: Brucella abortus 2308 derivatives with mini-Tn5 insertions in purE, purL, and purD display significant attenuation in the BALBc mouse model. It confirms the importance of the purine biosynthesis pathways for the survival and replication of the brucellae in host macrophages [Ref6485:Alcantara et al., 2004]. Studies with B melitensis purE and B abortus purL mutants, which are purine auxotrophs, and B suis aroC mutants, which can not synthesize aromatic amino acids, indicate that the brucellae also face signicant nutrient limitation during their prolonged residence in host macrophages [Ref6485:Alcantara et al., 2004]. |
15271960
|
|
|
glyA from Brucella melitensis bv. 1 str. 16M |
Brucella melitensis bv. 1 str. 16M |
1196903
|
|
17987475
|
BMEI1192 |
|
NP_540109.1 |
SERINE HYDROXYMETHYLTRANSFERASE |
Virulence factor |
FUNCTION: Interconversion of serine and glycine(Swiss-Prot: Q8G1F1).
CATALYTIC ACTIVITY: 5,10-methylenetetrahydrofolate + glycine + H(2)O = tetrahydrofolate + L-serine(Swiss-Prot: Q8G1F1).
COFACTOR: Pyridoxal phosphate (By similarity)(Swiss-Prot: Q8G1F1).
PATHWAY: Key enzyme in the biosynthesis of purines, lipids, hormones and other components(Swiss-Prot: Q8G1F1).
SUBUNIT: Homotetramer (By similarity)(Swiss-Prot: Q8G1F1).
SUBCELLULAR LOCATION: Cytoplasm (By similarity)(Swiss-Prot: Q8G1F1).
SIMILARITY: Belongs to the SHMT family(Swiss-Prot: Q8G1F1).
MUTATION: A study with miniTn5 mutants of B. suis constitutively expressing gfp indicates that B. suis glyA gene is required for intracellular multiplication in human macrophage THP-1 cells [Ref412:Kohler et al., 2002]. |
12438693
|
|
|
BMEI1229 |
Brucella |
1196940
|
|
17987512
|
BMEI1229 |
|
NP_540146.1 |
Hypothetical exonuclease |
Virulence factor |
FUNCTIONAL GROUP: Unkown function [Ref6462:Delrue et al., 2004].
FUNCTION: Exonuclease X-T domain [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Mice [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
galE from Brucella melitensis bv. 1 str. 16M |
Brucella melitensis bv. 1 str. 16M |
1196948
|
|
17987520
|
BMEI1237 |
|
NP_540154.1 |
UDP-GLUCOSE 4-EPIMERASE |
Virulence factor |
FUNCTIONAL GROUP: a.a. metabolism, Unkown [Ref6462:Delrue et al., 2004].
FUNCTION: UDP-glucose 4-epimerase [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
purM from Brucella melitensis bv. 1 str. 16M |
Brucella melitensis bv. 1 str. 16M |
1196951
|
|
17987523
|
BMEI1240 |
|
NP_540157.1 |
phosphoribosylaminoimidazole synthetase |
Virulence factor |
CATALYTIC ACTIVITY: ATP + 2-(formamido)-N(1)-(5-phospho-D-ribosyl)acetamidine = ADP + phosphate + 5-amino-1-(5-phospho-D-ribosyl)imidazole(Swiss-Prot: Q8G1K5).
PATHWAY: Nucleotide biosynthesis; IMP biosynthesis; 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide from N(2)-formyl-N(1)-(5-phospho-D-ribosyl)glycinamide: step 2(Swiss-Prot: Q8G1K5).
PATHWAY: Context: Purine biosynthesis(Swiss-Prot: Q8G1K5).
SUBCELLULAR LOCATION: Cytoplasm (By similarity)(Swiss-Prot: Q8G1K5).
SIMILARITY: Belongs to the AIR synthase family(Swiss-Prot: Q8G1K5).
MUTATION: B. abortus purM gene is essential for intracellular growth in HeLa cells as shown from transposon mutagenesis study [Ref6469:Kim et al., 2003]. |
12761078
|
|
|
purN from Brucella melitensis bv. 1 str. 16M |
Brucella melitensis bv. 1 str. 16M |
1196952
|
|
17987524
|
BMEI1241 |
|
NP_540158.1 |
phosphoribosylglycinamide formyltransferase |
Virulence factor |
MUTATION: B. abortus purN gene is essential for intracellular growth in HeLa cells as shown from transposon mutagenesis study [Ref6469:Kim et al., 2003]. |
12761078
|
|
|
omp25 from Brucella melitensis bv. 1 str. 16M |
Brucella melitensis bv. 1 str. 16M |
1196960
|
|
17987532
|
BMEI1249 |
|
NP_540166.1 |
25 KDA OUTER-MEMBRANE IMMUNOGENIC PROTEIN PRECURSOR |
Virulence factor |
SUBCELLULAR LOCATION: Outer membrane(Swiss-Prot: Q45689).
SIMILARITY: Belongs to the omp25/ropB family(Swiss-Prot: Q45689).
MUTATION: In contrast to WT B suis or Deltaomp31 B suis, Deltaomp25 B suis induced TNF-alpha production when phagocytosed by human macrophages. So Omp25 of B suis is involved in the negative regulation of TNF-alpha production upon infection of human macrophages [Ref6492:Jubier-Maurin et al., 2001].
To determine the role of Omp25 in virulence, mutants were created with Brucella abortus (BA25), Brucella melitensis (BM25), and Brucella ovis (BO25) which contain disruptions in the omp25 gene (Deltaomp25 mutants). BALBc mice infected with B abortus BA25 or B melitensis BM25 showed a significant decrease in mean CFUspleen at 18 and 4 weeks post-infection, respectively, when compared to the virulent parental strain. Mice infected with B ovis BO25 had significantly lower mean CFUspleen counts from 1 to 8 weeks post-infection, at which point the mutant was cleared from the spleens. Murine vaccination with either BM25 or the current caprine vaccine B melitensis strain Rev.1 resulted in more than a 2log (10) reduction in bacterial load following challenge with virulent B melitensis. Vaccination of mice with the B ovis mutant resulted in clearance of the challenge strain and provided 2.5log (10) greater protection against virulent B ovis than vaccine strain Rev.1. Based on these data, the B melitensis and B ovis Deltaomp25 mutants are interesting vaccine candidates that are currently under study in our laboratory for their safety and efficacy in small ruminants [Ref6492:Jubier-Maurin et al., 2001].
Although they are slightly attenuated, B abortus omp25 and omp22 mutants do not show the high level of attenuation and sensitivity to bactericidal peptides displayed by the bvrS and bvrR mutants [Ref6492:Jubier-Maurin et al., 2001]. B abortus mutants carrying Omp25 deletions do not show enrichment of underacylated LPS [Ref6492:Jubier-Maurin et al., 2001].
Brucella spp. omp25 deletion mutants are attenuated in mice, cattle and goats, showing the involvement of Brucella spp. Omp25 in virulence [Ref6492:Jubier-Maurin et al., 2001]. |
11447156
|
|
|
BMEI1258 |
Brucella |
1196969
|
|
17987541
|
BMEI1258 |
|
NP_540175.1 |
ABC TRANSPORTER ATP-BINDING PROTEIN |
Virulence factor |
FUNCTIONAL GROUP: "Classical virulence factors", Secretion of transport system, Transpter [Ref6462:Delrue et al., 2004].
FUNCTION: ABC transporter [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Differential fluorescence induction [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
pyrC from Brucella melitensis bv. 1 str. 16M |
Brucella melitensis bv. 1 str. 16M |
1196992
|
|
17987564
|
BMEI1281 |
|
NP_540198.1 |
dihydroorotase |
Virulence factor |
FUNCTIONAL GROUP: DNA/RNA metabolism, Synthesis [Ref6462:Delrue et al., 2004].
FUNCTION: dihydroorotase [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
spotT from Brucella melitensis bv. 1 str. 16M |
Brucella melitensis bv. 1 str. 16M |
1197007
|
|
17987579
|
BMEI1296 |
|
NP_540213.1 |
GUANOSINE-3',5'-BIS(DIPHOSPHATE) 3'-PYROPHOSPHOHYDROLASE |
Virulence factor |
FUNCTIONAL GROUP: Regulation [Ref6462:Delrue et al., 2004].
FUNCTION: ppGpp synthetase [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
lpsA from Brucella melitensis bv. 1 str. 16M |
Brucella melitensis bv. 1 str. 16M |
1197037
|
|
17987609
|
BMEI1326 |
|
NP_540243.1 |
LPSA PROTEIN |
Virulence factor |
FUNCTIONAL GROUP: "Classical virulence factors", Envelope molecules, Lipopolysaccharide [Ref6462:Delrue et al., 2004].
FUNCTION: putative glycosyltranferase [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Macrophages [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
htrA from Brucella melitensis bv. 1 str. 16M |
Brucella melitensis bv. 1 str. 16M |
1197041
|
|
17987613
|
BMEI1330 |
|
NP_540247.1 |
PROTEASE DO |
Virulence factor |
FUNCTIONAL GROUP: Stress proteins/Chaperones [Ref412:Kohler et al., 2002].
FUNCTION: Protease [Ref412:Kohler et al., 2002].
MUTATION: Attenuated in "Goat", Macrophages, but not in Mice [Ref412:Kohler et al., 2002]. |
12438693
|
|
|
feuQ from Brucella melitensis bv. 1 str. 16M |
Brucella melitensis bv. 1 str. 16M |
1197047
|
|
17987619
|
BMEI1336 |
|
NP_540253.1 |
SENSOR PROTEIN PHOQ |
Virulence factor |
FUNCTIONAL GROUP: Regulation [Ref6462:Delrue et al., 2004].
FUNCTION: Histidine kinase [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
feuP from Brucella melitensis bv. 1 str. 16M |
Brucella melitensis bv. 1 str. 16M |
1197048
|
|
17987620
|
BMEI1337 |
|
NP_540254.1 |
TRANSCRIPTIONAL REGULATORY PROTEIN PHOP |
Virulence factor |
FUNCTIONAL GROUP: Regulation [Ref6462:Delrue et al., 2004].
FUNCTION: Response regulator [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Mice, Macrophages [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
BMEI1339 |
Brucella |
1197050
|
|
17987622
|
BMEI1339 |
|
NP_540256.1 |
hypothetical protein |
Virulence factor |
FUNCTIONAL GROUP: Unkown function [Ref6462:Delrue et al., 2004].
FUNCTION: Brucella/Agrobacterium orphan gene [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
BMEI1361 |
Brucella |
1197072
|
|
17987644
|
BMEI1361 |
|
NP_540278.1 |
Hypothetical Cytosolic Protein |
Virulence factor |
FUNCTIONAL GROUP: Unkown function [Ref6462:Delrue et al., 2004].
FUNCTION: [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Mice [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
wbpZ from Brucella melitensis bv. 1 str. 16M |
Brucella melitensis bv. 1 str. 16M |
1197104
|
|
17987676
|
BMEI1393 |
|
NP_540310.1 |
MANNOSYLTRANSFERASE C |
Virulence factor |
FUNCTIONAL GROUP: "Classical virulence factors", Envelope molecules, Lipopolysaccharide [Ref6462:Delrue et al., 2004].
FUNCTION: O-chain biosynthesis [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Mice, Macrophages [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
pmm from Brucella melitensis bv. 1 str. 16M |
Brucella melitensis bv. 1 str. 16M |
1197107
|
|
17987679
|
BMEI1396 |
|
NP_540313.1 |
PHOSPHOMANNOMUTASE |
Virulence factor |
FUNCTIONAL GROUP: "Classical virulence factors", Envelope molecules, Lipopolysaccharide [Ref6462:Delrue et al., 2004].
FUNCTION: O-chain biosynthesis [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
wbkA from Brucella melitensis bv. 1 str. 16M |
Brucella melitensis bv. 1 str. 16M |
1197115
|
|
17987687
|
BMEI1404 |
|
NP_540321.1 |
MANNOSYLTRANSFERASE |
Virulence factor |
FUNCTIONAL GROUP: "Classical virulence factors", Envelope molecules, Lipopolysaccharide [Ref6462:Delrue et al., 2004].
FUNCTION: O-chain biosynthesis [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Mice [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
rfbD from Brucella melitensis bv. 1 str. 16M |
Brucella melitensis bv. 1 str. 16M |
1197124
|
|
17987696
|
BMEI1413 |
|
NP_540330.1 |
GDP-mannose 4,6-dehydratase |
Virulence factor |
FUNCTIONAL GROUP: "Classical virulence factors", Envelope molecules, Lipopolysaccharide [Ref6462:Delrue et al., 2004].
FUNCTION: O-chain biosynthesis [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Mice, Macrophages [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
perA from Brucella melitensis bv. 1 str. 16M |
Brucella melitensis bv. 1 str. 16M |
1197125
|
|
17987697
|
BMEI1414 |
|
NP_540331.1 |
PEROSAMINE SYNTHETASE |
Virulence factor |
FUNCTIONAL GROUP: "Classical virulence factors", Envelope molecules, Lipopolysaccharide [Ref6462:Delrue et al., 2004].
FUNCTION: O-chain biosynthesis [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Macrophages [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
wbpL from Brucella melitensis bv. 1 str. 16M |
Brucella melitensis bv. 1 str. 16M |
1197137
|
|
17987709
|
BMEI1426 |
|
NP_540343.1 |
PUTATIVE UNDECAPRENYL-PHOSPHATE ALPHA-N-ACETYLGLUCOSAMINYLTRANSFERASE |
Virulence factor |
FUNCTIONAL GROUP: "Classical virulence factors", Envelope molecules, Lipopolysaccharide [Ref6462:Delrue et al., 2004].
FUNCTION: O-chain biosynthesis [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Mice, Macrophages [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
dsbA from Brucella melitensis bv. 1 str. 16M |
Brucella melitensis bv. 1 str. 16M |
1197151
|
|
17987723
|
BMEI1440 |
|
NP_540357.1 |
THIOL:DISULFIDE INTERCHANGE PROTEIN DSBA |
Virulence factor |
FUNCTIONAL GROUP: Oxidoreduction [Ref6462:Delrue et al., 2004].
FUNCTION: Disulfide bond formation protein [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
BMEI1443 |
Brucella |
1197154
|
|
17987726
|
BMEI1443 |
|
NP_540360.1 |
2-HALOALKANOIC ACID DEHALOGENASE I |
Virulence factor |
FUNCTIONAL GROUP: Unkown function [Ref6462:Delrue et al., 2004].
FUNCTION: haloacid dehalogenase-like hydrolase domain [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
BMEI1448 |
Brucella |
1197159
|
|
17987731
|
BMEI1448 |
|
NP_540365.1 |
C-DI-GMP PHOSPHODIESTERASE A-RELATED PROTEIN |
Virulence factor |
FUNCTIONAL GROUP: Unkown function [Ref6462:Delrue et al., 2004].
FUNCTION: EAL domain [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
thrC from Brucella melitensis bv. 1 str. 16M |
Brucella melitensis bv. 1 str. 16M |
1197161
|
|
17987733
|
BMEI1450 |
|
NP_540367.1 |
threonine synthase |
Virulence factor |
FUNCTIONAL GROUP: a.a. metabolism, Synthesis [Ref6462:Delrue et al., 2004].
FUNCTION: Thre. Synthesis [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Macrophages [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
tldD from Brucella melitensis bv. 1 str. 16M |
Brucella melitensis bv. 1 str. 16M |
1197179
|
|
17987751
|
BMEI1468 |
|
NP_540385.1 |
TLDD PROTEIN |
Virulence factor |
FUNCTIONAL GROUP: DNA/RNA metabolism, Regulation [Ref6462:Delrue et al., 2004].
FUNCTION: Putative modulator of DNA gyrase [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Mice [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
purF from Brucella melitensis bv. 1 str. 16M |
Brucella melitensis bv. 1 str. 16M |
1197199
|
|
17987771
|
BMEI1488 |
|
NP_540405.1 |
amidophosphoribosyltransferase |
Virulence factor |
MUTATION: A B. suis purF mutation experiment suggests that the purine biosynthesis pathway contributes to intracellular growth [Ref6469:Kim et al., 2003]. |
12761078
|
|
|
dxps |
Brucella melitensis bv. 1 str. 16M |
1197209
|
|
17987781
|
BMEI1498 |
NZ_GG703778 |
NP_540415 |
1-deoxy-D-xylulose-5-phosphate synthase |
Virulence factor |
FUNCTIONAL GROUP: Vitamines cofactors [Ref6462:Delrue et al., 2004].
FUNCTION: Thiamine synthesis [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Differential fluorescence induction [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
aroC from Brucella melitensis bv. 1 str. 16M |
Brucella melitensis bv. 1 str. 16M |
1197217
|
|
17987789
|
BMEI1506 |
|
NP_540423.1 |
chorismate synthase |
Virulence factor |
CATALYTIC ACTIVITY: 5-O-(1-carboxyvinyl)-3-phosphoshikimate = chorismate + phosphate(Swiss-Prot: P63608).
COFACTOR: Reduced flavin (By similarity)(Swiss-Prot: P63608).
PATHWAY: Metabolic intermediate biosynthesis; chorismate biosynthesis; chorismate from D-erythrose 4-phosphate and PEP: step 7 [final step](Swiss-Prot: P63608).
PATHWAY: Context: Aromatic amino acids biosynthesis(Swiss-Prot: P63608).
SUBUNIT: Homotetramer (By similarity)(Swiss-Prot: P63608).
SIMILARITY: Belongs to the chorismate synthase family(Swiss-Prot: P63608).
MUTATION: The cloned aroC gene complements Escherichia coli and Salmonella enterica serovar Typhimurium aroC mutants. A B suis aroC mutant was found to be unable to grow in a defined medium without aromatic compounds. The mutant was highly attenuated in it issue culture (THP1 macrophages and HeLa cells) and murine virulence models [Ref6488:Foulongne et al., 2001]. |
11119550
|
|
|
purD from Brucella melitensis bv. 1 str. 16M |
B rucella melitensis bv. 1 str. 16M |
1197230
|
|
17987802
|
BMEI1519 |
|
NP_540436.1 |
phosphoribosylamine--glycine ligase |
Virulence factor |
CATALYTIC ACTIVITY: ATP + 5-phospho-D-ribosylamine + glycine = ADP + phosphate + N(1)-(5-phospho-D-ribosyl)glycinamide(Swiss-Prot: Q8G2B1).
PATHWAY: Nucleotide biosynthesis; IMP biosynthesis; N(1)-(5-phospho-D-ribosyl)glycinamide from 5-phospho-alpha-D-ribose 1-diphosphate: step 2(Swiss-Prot: Q8G2B1).
PATHWAY: Context: Purine biosynthesis(Swiss-Prot: Q8G2B1).
SIMILARITY: Belongs to the GARS family(Swiss-Prot: Q8G2B1).
SIMILARITY: Contains 1 ATP-grasp domain(Swiss-Prot: Q8G2B1).
MUTATION: Brucella abortus 2308 derivatives with mini-Tn5 insertions in purE, purL, and purD display significant attenuation in the BALBc mouse model. It confirms the importance of the purine biosynthesis pathways for the survival and replication of the brucellae in host macrophages [Ref6485:Alcantara et al., 2004].
Like the purE mutant, a purD::Tn10 mutant has reduced survival in murine macrophages and reduced virulence in mice [Ref6485:Alcantara et al., 2004]. |
15271960
|
|
|
BMEI1531 |
Brucella |
1197242
|
|
17987814
|
BMEI1531 |
|
NP_540448.1 |
TETRATRICOPEPTIDE REPEAT FAMILY PROTEIN |
Virulence factor |
FUNCTIONAL GROUP: Other genes [Ref6462:Delrue et al., 2004].
FUNCTION: protein-protein interaction [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
bacA from Brucella melitensis bv. 1 str. 16M |
Brucella melitensis bv. 1 str. 16M |
1197264
|
|
17987836
|
BMEI1553 |
|
NP_540470.1 |
transport protein |
Virulence factor |
MUTATION: B abortus bacA mutant exhibited decreased survival in macrophages and greatly accelerated clearance from experimentally infected mice compared to the virulent parental strain [Ref6487:LeVier et al., 2000]. R meliloti bacA gene encodes a putative cytoplasmic membrane transport protein required for symbiosis [Ref6487:LeVier et al., 2000]. The BacA protein is essential for the long-term survival of Sinorhizobium meliloti and Brucella abortus within acidic compartments in plant and animal cells , respectively. Mutation study showed that B. abortus BacA affects the distribution of LPS fatty acids, including a very-long-chain fatty acid thought to be unique to the alpha-proteobacteria[Ref6533:Ferguson et al., 2002]. |
10741969
12270820
|
|
|
lysR18 |
Brucella |
1197284
|
|
17987856
|
BMEI1573 |
|
NP_540490.1 |
TRANSCRIPTIONAL REGULATORY PROTEIN, LYSR FAMILY |
Virulence factor |
FUNCTIONAL GROUP: lysR family [Ref6530:Haine et al., 2005].
MUTATION: Attenuated using plasmid-tagged mutagenesis method [Ref6530:Haine et al., 2005]. |
16113274
|
|
|
vsrB from Brucella melitensis bv. 1 str. 16M |
Brucella melitensis bv. 1 str. 16M |
1197317
|
|
17987889
|
BMEI1606 |
|
NP_540523.1 |
SENSORY TRANSDUCTION HISTIDINE KINASE |
Virulence factor |
FUNCTIONAL GROUP: Regulation [Ref6462:Delrue et al., 2004].
FUNCTION: Histidine kinase [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
pyrD from Brucella melitensis bv. 1 str. 16M |
Brucella melitensis bv. 1 str. 16M |
1197322
|
|
17987894
|
BMEI1611 |
|
NP_540528.1 |
dihydroorotate dehydrogenase 2 |
Virulence factor |
MUTATION: B. suis pyrD mutation study indicated that pyrimidine synthesis pathway contributes to intracellular growth [Ref6469:Kim et al., 2003]. |
12761078
|
|
|
pgi from Brucella melitensis bv. 1 str. 16M |
Brucella melitensis bv. 1 str. 16M |
1197347
|
|
17987919
|
BMEI1636 |
|
NP_540553.1 |
glucose-6-phosphate isomerase |
Virulence factor |
CATALYTIC ACTIVITY: D-glucose 6-phosphate = D-fructose 6-phosphate(Swiss-Prot: Q8G2N3).
PATHWAY: Carbohydrate degradation; glycolysis; D-glyceraldehyde 3-phosphate and glycerone phosphate from D-glucose: step 2(Swiss-Prot: Q8G2N3).
SUBCELLULAR LOCATION: Cytoplasm (By similarity)(Swiss-Prot: Q8G2N3).
SIMILARITY: Belongs to the GPI family(Swiss-Prot: Q8G2N3).
MUTATION: B. suis pgi is a gene identified by signature-tagged mutagenesis. The mutant is attenuated inside THP1 macrophages. The mutation of the pgi gene could also affect the biosynthesis of the bacterial peptidoglycan [Ref6484:Foulongne et al., 2000]. |
10678941
|
|
|
BMEI1658 |
Brucella |
1197369
|
|
17987941
|
BMEI1658 |
|
NP_540575.1 |
hypothetical protein |
Virulence factor |
FUNCTIONAL GROUP: Unkown function [Ref6462:Delrue et al., 2004].
FUNCTION: Brucella orphan gene [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Macrophages [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
hisD from Brucella melitensis bv. 1 str. 16M |
Brucella melitensis bv. 1 str. 16M |
1197379
|
|
17987951
|
BMEI1668 |
|
NP_540585.1 |
histidinol dehydrogenase |
Virulence factor |
FUNCTION: Catalyzes the sequential NAD-dependent oxidations of L-histidinol to L-histidinaldehyde and then to L-histidine (By similarity)(Swiss-Prot: Q8G2R2).
CATALYTIC ACTIVITY: L-histidinol + 2 NAD(+) = L-histidine + 2 NADH(Swiss-Prot: Q8G2R2).
COFACTOR: Binds 1 zinc ion per subunit (By similarity)(Swiss-Prot: Q8G2R2).
PATHWAY: Amino-acid biosynthesis; L-histidine biosynthesis; L-histidine from 5-phospho-alpha-D-ribose 1-diphosphate: step 9 [final step](Swiss-Prot: Q8G2R2).
SIMILARITY: Belongs to the histidinol dehydrogenase family(Swiss-Prot: Q8G2R2).
MUTATION: A study with miniTn5 mutants of B. suis constitutively expressing gfp indicates that B. suis hisD gene is required for intracellular multiplication in human macrophage THP-1 cells [Ref412:Kohler et al., 2002]. |
12438693
|
|
|
malK from Brucella melitensis bv. 1 str. 16M |
Brucella melitensis bv. 1 str. 16M |
1197424
|
|
17987996
|
BMEI1713 |
|
NP_540630.1 |
MALTOSE/MALTODEXTRIN TRANSPORT ATP-BINDING PROTEIN MALK |
Virulence factor |
FUNCTIONAL GROUP: a.a. metabolism, Transport [Ref6462:Delrue et al., 2004].
FUNCTION: Maltose transport [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Macrophages, but not in HeLa [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
exsA from Brucella melitensis bv. 1 str. 16M |
Brucella melitensis bv. 1 str. 16M |
1197453
|
|
17988025
|
BMEI1742 |
|
NP_540659.1 |
ABC TRANSPORTER ATP-BINDING PROTEIN |
Virulence factor |
FUNCTIONAL GROUP: a.a. metabolism, Transport [Ref6462:Delrue et al., 2004].
FUNCTION: ABC transporter [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Mice [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
metH from Brucella melitensis bv. 1 str. 16M |
Brucella melitensis bv. 1 str. 16M |
1197470
|
|
17988042
|
BMEI1759 |
|
NP_540676.1 |
B12-dependent methionine synthase |
Virulence factor |
FUNCTIONAL GROUP: a.a. metabolism, Synthesis [Ref6462:Delrue et al., 2004].
FUNCTION: Met. synthesis [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
cysI from Brucella melitensis bv. 1 str. 16M |
Brucella melitensis bv. 1 str. 16M |
1197477
|
|
17988049
|
BMEI1766 |
|
NP_540683.1 |
SULFITE REDUCTASE (FERREDOXIN) |
Virulence factor |
FUNCTIONAL GROUP: Oxidoreduction [Ref6462:Delrue et al., 2004].
FUNCTION: Sulfite reductate [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Mice, Macrophages, but not in HeLa [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
glnL |
Brucella melitensis bv. 1 str. 16M |
1197497
|
|
17988069
|
BMEI1786 |
NZ_GG703778 |
NP_540703 |
nitrogen regulatory IIA protein |
Virulence factor |
FUNCTIONAL GROUP: Regulation [Ref6462:Delrue et al., 2004].
FUNCTION: Nitrogen regulatory IIA [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Macrophages [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
glnD from Brucella melitensis bv. 1 str. 16M |
Brucella melitensis bv. 1 str. 16M |
1197515
|
|
17988087
|
BMEI1804 |
|
NP_540721.1 |
PII uridylyl-transferase |
Virulence factor |
FUNCTION: Modifies, by uridylylation or deuridylylation the PII (glnB) regulatory protein (By similarity)(Swiss-Prot: Q8G312).
CATALYTIC ACTIVITY: UTP + [protein-PII] = diphosphate + uridylyl-[protein-PII](Swiss-Prot: Q8G312).
SIMILARITY: Belongs to the glnD family(Swiss-Prot: Q8G312).
MUTATION: glnD encodes for a uridylyl transferase which is the primary sensor of nitrogen. The glnD mutant via signature-tagged transposon mutagenesis is attenuated in THP1 macrophages and HeLa cells. It supports the hypothesis that the concentration of glutamine in host cells is critical for the intracellular survival of Brucella [Ref6484:Foulongne et al., 2000]. |
10678941
|
|
|
BMEI1809 |
Brucella |
1197520
|
|
17988092
|
BMEI1809 |
|
NP_540726.1 |
PROTEIN YBIS PRECURSOR |
Virulence factor |
FUNCTIONAL GROUP: Unkown function [Ref6462:Delrue et al., 2004].
FUNCTION: ERFK/YBIS/YCFS/YNHG family [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
ndvB from Brucella melitensis bv. 1 str. 16M |
Brucella melitensis bv. 1 str. 16M |
1197548
|
|
17988120
|
BMEI1837 |
|
NP_540754.1 |
CELLOBIOSE-PHOSPHORYLASE |
Virulence factor |
FUNCTIONAL GROUP: a.a. metabolism, Unkown [Ref6462:Delrue et al., 2004].
FUNCTION: Synthesis of cyclic ( [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Mice, HeLa [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
BMEI1844 |
Brucella |
1197555
|
|
17988127
|
BMEI1844 |
|
NP_540761.1 |
hypothetical protein |
Virulence factor |
FUNCTIONAL GROUP: Unkown function [Ref6462:Delrue et al., 2004].
FUNCTION: Domain of Unkown Function (DUF930) [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
ilvD from Brucella melitensis bv. 1 str. 16M |
Brucella melitensis bv. 1 str. 16M |
1197559
|
|
17988131
|
BMEI1848 |
|
NP_540765.1 |
dihydroxy-acid dehydratase |
Virulence factor |
CATALYTIC ACTIVITY: 2,3-dihydroxy-3-methylbutanoate = 3-methyl-2-oxobutanoate + H(2)O(Swiss-Prot: Q8G353).
COFACTOR: Binds 1 4Fe-4S cluster (Potential)(Swiss-Prot: Q8G353).
PATHWAY: Amino-acid biosynthesis; L-isoleucine biosynthesis; L-isoleucine from 2-oxobutanoate: step 3(Swiss-Prot: Q8G353).
PATHWAY: Amino-acid biosynthesis; L-valine biosynthesis; L-valine from pyruvate: step 3(Swiss-Prot: Q8G353).
SIMILARITY: Belongs to the ilvD/edd family(Swiss-Prot: Q8G353).
MUTATION: Of those B abortus mutants with mini-Tn5 insertions in genes predicted to be involved in amino acid biosynthesis and transport, only the ilvD mutant, displayed attenuation in both macrophages and mice. The othre two amino acid biosynthesis mutants [trpB::miniTn5 and pheA::miniTn5] displayed wild-type virulence in mice but attenuated inside macrophages. The studies with B abortus ilvD, trpB, and pheA mutants suggest that tryptophan and phenylalanine are available to the brucellae in their intracellular niche but that other amino acids (eg, leucine, isoleucine, or valine) are not [Ref6485:Alcantara et al., 2004]. |
15271960
|
|
|
cysY |
Brucella melitensis bv. 1 str. 16M |
1197560
|
|
17988132
|
BMEI1849 |
NZ_GG703778 |
NP_540766 |
thiol:disulfide interchange protein CYCY precursor |
Virulence factor |
FUNCTIONAL GROUP: Oxidoreduction [Ref6462:Delrue et al., 2004].
FUNCTION: Disulfide oxidoreducate [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
BMEI1859 |
Brucella |
1197570
|
|
17988142
|
BMEI1859 |
|
NP_540776.1 |
INTEGRAL MEMBRANE PROTEIN |
Virulence factor |
FUNCTIONAL GROUP: Unkown function [Ref6462:Delrue et al., 2004].
FUNCTION: Uncharacterised protein family 0005 [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Macrophages [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
BMEI1879 |
Brucella |
1197590
|
|
17988162
|
BMEI1879 |
|
NP_540796.1 |
Hypothetical Cytosolic Protein |
Virulence factor |
FUNCTIONAL GROUP: Unkown function [Ref6462:Delrue et al., 2004].
FUNCTION: Brucella/Mesorhizobium orphan gene [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
pgm from Brucella melitensis bv. 1 str. 16M |
Brucella melitensis bv. 1 str. 16M |
1197597
|
|
17988169
|
BMEI1886 |
|
NP_540803.1 |
phosphoglucomutase |
Virulence factor |
MUTATION: Brucella pgm encodes the phosphoglucomutase. The B. abortus pgm mutant (B2211) lacks the O antigen. However, the core region of the mutant LPS migrated in Tricine-PAGE electrophoresis in a position that was indistinguishable from that of the wild type core. Although the exponential intracellular replication of the pgm mutant was delayed by approximately 20 h with respect to that of the wild type, the high number of recoverable bacteria at 48 h postinfection indicates that mutant strain B2211 replicates inside HeLa host cells [Ref6486:Ugalde et al., 2000].
B abortus phosphoglucomutase (pgm) insertional mutants were attenuated in vivo but not in vitro [Ref6534:Ko and Splitter, 2003]. |
10992476
12525425
|
|
|
BMEI1902 |
Brucella |
1197613
|
|
17988185
|
BMEI1902 |
|
NP_540819.1 |
Molybdopterin biosynthesis enzyme |
Virulence factor |
FUNCTIONAL GROUP: Unkown function [Ref6462:Delrue et al., 2004].
FUNCTION: Brucella/Mesorhizobium orphan gene [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
lysR13 |
Brucella |
1197624
|
|
17988196
|
BMEI1913 |
|
NP_540830.1 |
TRANSCRIPTIONAL REGULATORY PROTEIN, LYSR FAMILY |
Virulence factor |
FUNCTIONAL GROUP: lysR family [Ref6530:Haine et al., 2005].
MUTATION: Attenuated using plasmid-tagged mutagenesis method [Ref6530:Haine et al., 2005]. |
16113274
|
|
|
rpsA from Brucella melitensis bv. 1 str. 16M |
Brucella melitensis bv. 1 str. 16M |
1197626
|
|
17988198
|
BMEI1915 |
|
NP_540832.1 |
30S ribosomal protein S1 |
Virulence factor |
MUTATION: rpsA is a B. suis gene identified by signature-tagged mutagenesis [Ref6484:Foulongne et al., 2000]. |
10678941
|
|
|
mutM from Brucella melitensis bv. 1 str. 16M |
Brucella melitensis bv. 1 str. 16M |
1197657
|
|
17988229
|
BMEI1946 |
|
NP_540863.1 |
formamidopyrimidine-DNA glycosylase |
Virulence factor |
FUNCTION: Involved in base excision repair of DNA damaged by oxidation or by mutagenic agents. Acts as DNA glycosylase that recognizes and removes damaged bases. Has a preference for oxidized purines, such as 7,8-dihydro-8-oxoguanine (8-oxoG). Has AP (apurinic/apyrimidinic) lyase activity and introduces nicks in the DNA strand. Cleaves the DNA backbone by beta-delta elimination to generate a single-strand break at the site of the removed base with both 3'- and 5'-phosphates (By similarity)(Swiss-Prot: Q8FXR6).
CATALYTIC ACTIVITY: Hydrolysis of DNA containing ring-opened N(7)-methylguanine residues, releasing 2,6-diamino-4-hydroxy-5-(N-methyl)formamidopyrimidine(Swiss-Prot: Q8FXR6).
CATALYTIC ACTIVITY: The C-O-P bond 3' to the apurinic or apyrimidinic site in DNA is broken by a beta-elimination reaction, leaving a 3'-terminal unsaturated sugar and a product with a terminal 5'-phosphate(Swiss-Prot: Q8FXR6).
COFACTOR: Binds 1 zinc ion per subunit (By similarity)(Swiss-Prot: Q8FXR6).
SUBUNIT: Monomer (By similarity)(Swiss-Prot: Q8FXR6).
SIMILARITY: Belongs to the FPG family(Swiss-Prot: Q8FXR6).
SIMILARITY: Contains 1 FPG-type zinc finger(Swiss-Prot: Q8FXR6).
MUTATION: Attenuated in Differential fluorescence induction [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
dnaK from Brucella melitensis bv. 1 str. 16M |
Brucella melitensis bv. 1 str. 16M |
1197713
|
|
17988285
|
BMEI2002 |
|
NP_540919.1 |
molecular chaperone DnaK |
Virulence factor |
FUNCTION: Acts as a chaperone (By similarity)(Swiss-Prot: Q8FXX2).
INDUCTION: By stress conditions e.g. heat shock (By similarity)(Swiss-Prot: Q8FXX2).
SIMILARITY: Belongs to the heat shock protein 70 family(Swiss-Prot: Q8FXX2).
MUTATION: The heat shock protein DnaK is essential for intramacrophagic replication of Brucella suis. The replacement of the stress-inducible, native dnaK promoter of B suis by the promoter of the constitutively expressed bla gene resulted in temperature-independent synthesis of DnaK. In contrast to a dnaK null mutant, this strain grew at 37 degrees C, with a thermal cutoff at 39 degrees C However, the constitutive dnaK mutant, which showed high sensitivity to H(2)O(2)-mediated stress , failed to multiply in murine macrophage-like cells and was rapidly eliminated in a mouse model of infection, adding strong arguments that stress-mediated and heat shock promoter-dependent induction of dnaK is a crucial event in the intracellular replication of B suis [Ref6500:Köhler et al., 2002].
Mutation studies indicated that DnaK, but not DnaJ, was required for growth at 37 degrees C in vitro. Viability of the dnaK null mutant was also greatly affected at low pH. In infection experiments performed with both mutants at the reduced temperature of 30 degrees C, the dnaK mutant of B suis survived but failed to multiply within U937 cells, whereas the wild-type strain and the dnaJ mutant multiplied normally. Complementation of the dnaK mutant with the cloned dnaK gene restored growth at 37 degrees C, increased resistance to acid pH, and increased intracellular multiplication [Ref6500:Köhler et al., 2002]. |
11854256
|
|
|
bvrS from Brucella melitensis bv. 1 str. 16M |
Brucella melitensis bv. 1 str. 16M |
1197746
|
|
17988318
|
BMEI2035 |
|
NP_540952.1 |
SENSOR PROTEIN CHVG |
Virulence factor |
MUTATION: The two-component BvrSBvrR system is essential for Brucella abortus virulence. Disruption of BvrSBvrR damages the outer membrane, thus contributing to the severe attenuation manifested by bvrS and bvrR mutants. The bvrS and bvrR mutants are avirulent in mice, show reduced invasiveness to epithelial cells and macrophages, and are incapable of inhibiting lysosome fusion and replicating intracellularly [Ref6535:Manterola et al., 2005].
Mutations in the bvrR or bvrS genes hamper the penetration of B abortus in non-phagocytic cells and impairs intracellular trafficking and virulence. BvrRBvrS mutants do not recruit small GTPases of the Rho subfamily required for actin polymerization and penetration to cells. Dysfunction of the BvrRBvrS system alters the outer membrane permeability, the expression of several group 3 outer membrane proteins and the pattern of lipid A acylation. Constructs of virulent B abortus chimeras containing heterologous LPS from the bvrS(-) mutant demonstrated an altered permeability to cationic peptides similar to that of the BvrRBvrS mutants. It is hypothesized that the Brucella BvrRBvrS is a system devoted to the homeostasis of the outer membrane and, therefore in the interface for cell invasion and mounting the required structures for intracellular parasitism [Ref6536:López-Goñi et al., 2002].
In contrast to S2308 and S19, bvrS and bvrR mutant strains poorly invade HeLa cells and are rapidly targeted to cathepsin D- containing compartments [Ref6537:Pizarro-Cerdá et al., 1998].
B abortus bvrS bvrR mutants display reduced invasiveness and virulence [Ref6538:Briones et al., 2001].
Brucella bvrS and bvrR null mutants are defective in several outer membrane proteins, mainly Omp3a (former Omp25) and Omp3b as well as in the structure of the LPS molecule, but the O chain seems to be intact [Ref6466:Gorvel and Moreno, 2002].
Because bvrR and bvrS mutants are also altered in cell-surface hydrophobicity, permeability, and sensitivity to surface- targeted bactericidal peptides, it is proposed that BvrRBvrS controls cell envelope changes necessary to transit between extracellular and intracellular environments [Ref6499:Guzman-Verri et al., 2002].
BvrR/BvrS mutants are avirulent in mice, show reduced invasiveness in cells, and are unable to inhibit lysosome fusion and to replicate intracellularly [Ref6499:Guzman-Verri et al., 2002]. |
16077108
12414153
9826346
11401996
12414149
12218183
|
|
|
bvrR from Brucella melitensis bv. 1 str. 16M |
Brucella melitensis bv. 1 str. 16M |
1197747
|
|
17988319
|
BMEI2036 |
|
NP_540953.1 |
TRANSCRIPTIONAL REGULATORY PROTEIN CHVI |
Virulence factor |
MUTATION: The two-component BvrSBvrR system is essential for Brucella abortus virulence. Disruption of BvrSBvrR damages the outer membrane, thus contributing to the severe attenuation manifested by bvrS and bvrR mutants. The bvrS and bvrR mutants are avirulent in mice, show reduced invasiveness to epithelial cells and macrophages, and are incapable of inhibiting lysosome fusion and replicating intracellularly [Ref6535:Manterola et al., 2005].
Mutations in the bvrR or bvrS genes hamper the penetration of B abortus in non-phagocytic cells and impairs intracellular trafficking and virulence. BvrRBvrS mutants do not recruit small GTPases of the Rho subfamily required for actin polymerization and penetration to cells. Dysfunction of the BvrRBvrS system alters the outer membrane permeability, the expression of several group 3 outer membrane proteins and the pattern of lipid A acylation. Constructs of virulent B abortus chimeras containing heterologous LPS from the bvrS(-) mutant demonstrated an altered permeability to cationic peptides similar to that of the BvrRBvrS mutants. It is hypothesized that the Brucella BvrRBvrS is a system devoted to the homeostasis of the outer membrane and, therefore in the interface for cell invasion and mounting the required structures for intracellular parasitism [Ref6536:López-Goñi et al., 2002].
In contrast to S2308 and S19, bvrS and bvrR mutant strains poorly invade HeLa cells and are rapidly targeted to cathepsin D- containing compartments [Ref6537:Pizarro-Cerdá et al., 1998].
B abortus bvrS bvrR mutants display reduced invasiveness and virulence [Ref6538:Briones et al., 2001].
Brucella bvrS and bvrR null mutants are defective in several outer membrane proteins, mainly Omp3a (former Omp25) and Omp3b as well as in the structure of the LPS molecule, but the O chain seems to be intact [Ref6466:Gorvel and Moreno, 2002].
Because bvrR and bvrS mutants are also altered in cell-surface hydrophobicity, permeability, and sensitivity to surface- targeted bactericidal peptides, it is proposed that BvrRBvrS controls cell envelope changes necessary to transit between extracellular and intracellular environments [Ref6499:Guzman-Verri et al., 2002].
BvrR/BvrS mutants are avirulent in mice, show reduced invasiveness in cells, and are unable to inhibit lysosome fusion and to replicate intracellularly [Ref6499:Guzman-Verri et al., 2002]. |
16077108
12414153
9826346
11401996
12414149
12218183
|
|
|
hisF from Brucella melitensis bv. 1 str. 16M |
Brucella melitensis bv. 1 str. 16M |
1197752
|
|
17988324
|
BMEI2041 |
|
NP_540958.1 |
imidazole glycerol phosphate synthase subunit HisF |
Virulence factor |
FUNCTION: IGPS catalyzes the conversion of PRFAR and glutamine to IGP, AICAR and glutamate. The hisF subunit catalyzes the cyclization activity that produces IGP and AICAR from PRFAR using the ammonia provided by the hisH subunit (By similarity)(Swiss-Prot: Q8FY07).
CATALYTIC ACTIVITY: 5-[(5-phospho-1-deoxyribulos-1-ylamino)methylideneamino]-1-(5-phosphoribosyl)imidazole-4-carboxamide + L-glutamine = imidazole-glycerol phosphate + 5-aminoimidazol-4-carboxamide ribonucleotide + L-glutamate + H(2)O(Swiss-Prot: Q8FY07).
PATHWAY: Amino-acid biosynthesis; L-histidine biosynthesis; L-histidine from 5-phospho-alpha-D-ribose 1-diphosphate: step 5(Swiss-Prot: Q8FY07).
SUBUNIT: Heterodimer of hisH and hisF (By similarity)(Swiss-Prot: Q8FY07).
SUBCELLULAR LOCATION: Cytoplasm (By similarity)(Swiss-Prot: Q8FY07).
SIMILARITY: Belongs to the hisA/hisF family(Swiss-Prot: Q8FY07).
MUTATION: A study with miniTn5 mutants of B. suis constitutively expressing gfp indicates that B. suis hisF gene is required for intracellular multiplication in human macrophage THP-1 cells [Ref412:Kohler et al., 2002]. |
12438693
|
|
|
omp10 from Brucella melitensis bv. 1 str. 16M |
Brucella melitensis bv. 1 str. 16M |
1197788
|
|
17988361
|
BMEII0017 |
|
NP_540994.1 |
OUTER MEMBRANE LIPOPROTEIN |
Virulence factor |
SUBCELLULAR LOCATION: Outer membrane; lipid-anchor(Swiss-Prot: P0A3N9).
MISCELLANEOUS: Elicits an immune response in B.melitensis-infected sheep but not in B.abortus-infected cattle(Swiss-Prot: P0A3N9).
SIMILARITY: Belongs to the rhizobiaceae omp10 lipoprotein family(Swiss-Prot: P0A3N9).
MUTATION: Omp10 is an immunoreactive outer membrane lipoprotein. The omp10 mutant was dramatically attenuated for survival in mice and was defective for growth in minimal medium but was not impaired in intracellular growth in vitro, nor does it display clear modification of the outer membrane properties [Ref6473:Tibor et al., 2002]. |
12228280
|
|
|
hemH from Brucella melitensis bv. 1 str. 16M |
Brucella melitensis bv. 1 str. 16M |
1197789
|
|
17988362
|
BMEII0018 |
|
NP_540995.1 |
ferrochelatase |
Virulence factor |
FUNCTION: Catalyzes the ferrous insertion into protoporphyrin IX(Swiss-Prot: P0A3D7).
CATALYTIC ACTIVITY: Protoporphyrin + Fe(2+) = protoheme + 2 H(+)(Swiss-Prot: P0A3D7).
PATHWAY: Protoheme biosynthesis; last step(Swiss-Prot: P0A3D7).
SUBCELLULAR LOCATION: Cytoplasm (By similarity)(Swiss-Prot: P0A3D7).
SIMILARITY: Belongs to the ferrochelatase family(Swiss-Prot: P0A3D7).
MUTATION: A hemH knockout B. abortus mutant displayed auxotrophy for hemin, defective intracellular survival inside J774 and HeLa cells, and lack of virulence in BALBc mice. This phenotype was overcome by complementing the mutant strain with a plasmid harboring wild-type hemH. These data demonstrate that B abortus synthesizes its own heme and also has the ability to use an external source of heme [Ref6472:Almirón et al., 2001]. |
11553564
|
|
|
virb1 |
Brucella melitensis bv. 1 str. 16M |
1197796
|
|
17988369
|
BMEII0025 |
AE008918 |
NP_541002 |
attachment mediating protein VIRB1-like protein |
Virulence factor |
MUTATION: The Brucella abortus virB operon, encoding a type IV secretion system (T4SS), is required for intracellular replication and persistent infection in the mouse model. The products of the first two genes of the virB operon, virB1 and virB2, are predicted to be localized at the bacterial surface. Both mutants were shown to be nonpolar, as demonstrated by their ability to express the downstream gene virB5 during stationary phase of growth in vitro. Both VirB1 and VirB2 were essential for intracellular replication in J774 macrophages. The nonpolar virB1 mutant persisted at wild-type levels, showing that the function of VirB1 is dispensable in the mouse model of persistent infection [Ref6539:den et al., 2004].
A B abortus polar virB1 mutant failed to replicate in HeLa cells, indicating that the virB operon plays a critical role in intracellular multiplication [Ref6540:Sieira et al., 2000].
Polar mutations in the virB1 to virB2 intergenic region or in virB2 reduced the detection of VirB5 to a greater extent than they did that of VirB12. A virB1 mutation also eliminates the transcription of virB12 in B suis [Ref6470:Sun et al., 2005].
An infection assay with signature-tagged Brucella abortus mutants demonstrated that mutagenesis of the virB1 gene causes attenuation of virulence [Ref6471:Höppner et al., 2005]. |
15322008
10940027
16113325
16272371
|
|
|
virB2 from Brucella melitensis bv. 1 str. 16M |
Brucella melitensis bv. 1 str. 16M |
1197797
|
|
17988370
|
BMEII0026 |
|
NP_541003.1 |
VirB2 |
Virulence factor |
MUTATION: The Brucella abortus virB operon, encoding a type IV secretion system (T4SS), is required for intracellular replication and persistent infection in the mouse model. The products of the first two genes of the virB operon, virB1 and virB2, are predicted to be localized at the bacterial surface. Both mutants were shown to be nonpolar, as demonstrated by their ability to express the downstream gene virB5 during stationary phase of growth in vitro. Both VirB1 and VirB2 were essential for intracellular replication in J774 macrophages. The nonpolar virB2 mutant was unable to cause persistent infection in the mouse model, demonstrating the essential role of VirB2 in the function of the T4SS apparatus during infection [Ref6539:den et al., 2004].
Polar mutations in the virB1 to virB2 intergenic region or in virB2 reduced the detection of VirB5 to a greater extent than they did that of VirB12. A virB1 mutation also eliminates the transcription of virB12 in B suis [Ref6470:Sun et al., 2005]. |
15322008
16113325
|
|
|
virB3 from Brucella melitensis bv. 1 str. 16M |
Brucella melitensis bv. 1 str. 16M |
1197798
|
|
17988371
|
BMEII0027 |
|
NP_541004.1 |
VirB3 |
Virulence factor |
MUTATION: The B abortus virB3 gene is found to be essential for intracellular growth inside HeLa cells [Ref6469:Kim et al., 2003]. |
12761078
|
|
|
virb4 from Brucella melitensis bv. 1 str. 16M |
Brucella melitensis bv. 1 str. 16M |
1197799
|
|
17988372
|
BMEII0028 |
|
NP_541005.1 |
ATPASE VIRB4 HOMOLOG |
Virulence factor |
MUTATION: A mutant strain of B abortus that contains an in-frame deletion in virB4 is unable to replicate in macrophages and survives in mice [Ref6541:Watarai et al., 2002]. ntracellular replication was inhibited in wild-type B abortus after introducing a plasmid expressing a mutant VirB4 altered in the NTP -binding region. VirB4 containing the intact NTP -binding region is essential for evasion of fusion with lysosomes (11988518).
The ruffling associated with internalization of the virB4 mutant results in a more rapid uptake than for the wild-type strain. The virB4 mutant shows primarily small regions of phalloidin staining at the sites of binding. Macrophages incubated simultaneously with B abortus and the fluid-phase marker tetramethyl rhodamine isothiocyanate (TRITC)-dextran accumulate the marker in large vacuoles containing the wild-type strain, but little or no marker accumulates in phagosomes containing the virB4 mutant. Similarly, phase-contrast micrographs have shown the wild-type strain in large phase-transparent compartments, but the virB4 mutant is in much smaller compartments (14738898).
Intracellular growth-defective virB4 mutant and attenuated vaccine strain S19 did not induce abortion [Ref6542:Kim et al., 2005].
The B abortus virB4 mutant was completely cleared from the spleens of mice after 4 weeks, while the pncA mutant showed a 1.5-log reduction of the number of bacteria isolated from spleens after 10 weeks. Splenomegaly was not observed at all in mice infected with virB4 mutant [Ref6468:Kim et al., 2004]. |
11988518
15869716
15135535
|
|
|
virB5 from Brucella melitensis bv. 1 str. 16M |
Brucella melitensis bv. 1 str. 16M |
1197800
|
|
17988373
|
BMEII0029 |
|
NP_541006.1 |
VirB5 |
Virulence factor |
MUTATION: A comparison of the VirB8 and VirB5 contents after induction of the B suis wild type and of virB5 and virB12 mutants further confirmed that the virB5 and virB12 genes belong to the same operon [Ref6543:Rouot et al., 2003].
Smooth strains of Brucella unable to replicate (ie, killed B suis or the avirulent mutant B suis virB5) exhibit delayed phagosome-lysosome fusion [Ref6544:Porte et al., 2003].
Polar mutations in the operon upstream of virB5 exert a greater effect on the expression of virB5 than they do on the expression of the downstream gene virB12. It indicates that in B abortus , regulatory elements other than the virB promoter may influence VirB12 protein levels [Ref6470:Sun et al., 2005].
Four independent mutants in virB5, virB9 or virB10 were highly attenuated in an in vitro infection model with human macrophages [Ref6467:O'Callaghan et al., 1999]. |
12595417
12595466
16113325
10510235
|
|
|
virb6 from Brucella melitensis bv. 1 str. 16M |
Brucella melitensis bv. 1 str. 16M |
1197801
|
|
17988374
|
BMEII0030 |
|
NP_541007.1 |
CHANNEL PROTEIN VIRB6 HOMOLOG |
Virulence factor |
MUTATION: B. abortus virB6 is essential for intracellular growth within HeLa cells as shown from a mutagenesis study. |
|
|
|
virB8 from Brucella melitensis bv. 1 str. 16M |
Brucella melitensis bv. 1 str. 16M |
1197803
|
|
17988376
|
BMEII0032 |
|
NP_541009.1 |
VirB8 |
Virulence factor |
MUTATION: virB8 mutant was attenuated by a mini-Tn5 transposon mutagenesis [Ref6484:Foulongne et al., 2000]. Attenuated non-polar virB2, virB4, virB8, virB9 and virB10 Brucella mutants are capable of penetrating cells as the same rate as the virulent wild-type Brucella, transit through EEA1-positive early compartments and then localize in LAMP1-positive compartments at early times of infection [Ref6466:Gorvel and Moreno, 2002]. |
10678941
12414149
|
|
|
virb9 from Brucella melitensis bv. 1 str. 16M |
Brucella melitensis bv. 1 str. 16M |
1197804
|
|
17988377
|
BMEII0033 |
|
NP_541010.1 |
CHANNEL PROTEIN VIRB9 HOMOLOG |
Virulence factor |
MUTATION: Uptake in the presence or absence of Ca2 and Mg2 did not influence the subsequent intracellular survival of wild-type Brucella, whereas the decrease in the number of surviving virB9 mutant cells was delayed in the absence of Ca2 and Mg2. Possibly two types of adhesion molecules promoted uptake of Brucella, one being Ca2 and Mg2 dependent and the other not, and that both types participate in the uptake of wild-type bacteria but only the latter type participates in the uptake of the virB9 mutant [Ref6545:Rittig et al., 2001].
Four independent mutants in virB5, virB9 or virB10 were highly attenuated in an in vitro infection model with human macrophages [Ref6467:O'Callaghan et al., 1999].
The intracellular fate of three virB mutants (virB2, virB4 and virB9) in HeLa cells by immunofluorescence was examined. The three VirB proteins are not necessary for penetration and the inhibition of phago-lysosomal fusion within non-professional phagocytes. Rather, the virB mutants are unable to reach the replicative niche and reside in a membrane -bound vacuole expressing the late endosomal marker, LAMP1, and the sec61beta protein from the ER membrane, proteins that are present in autophagic vesicles originating from the ER [Ref6546:Delrue et al., 2001].
Attenuated non-polar virB2, virB4, virB8, virB9 and virB10 Brucella mutants are capable of penetrating cells as the same rate as the virulent wild-type Brucella, transit through EEA1 -positive early compartments and then localize in LAMP1-positive compartments at early times of infection [Ref6466:Gorvel and Moreno, 2002]. |
11349069
10510235
11437834
12414149
|
|
|
virb10 |
Brucella melitensis bv. 1 str. 16M |
1197805
|
|
17988378
|
BMEII0034 |
AE008918 |
NP_541011 |
channel protein VIRB10-like protein |
Virulence factor |
MUTATION: Mutants with polar and nonpolar mutations introduced in irB10 showed different behaviors in mice and in the HeLa cell infection assay, suggesting that virB10 per se is necessary for the correct function of this type IV secretion apparatus [Ref6540:Sieira et al., 2000].
A B. abortus virB10 mutant showed a decrease of intracellular live bacteria comparable to that of the wild-type strain until 4 h after infection, indicating that a functional VirB system is not required for the short-term survival of Brucella inside macrophages. At later time points, the number of live virB10 mutants progressively decreased. Hence, the Brucella virB10 strain did not replicate, but rather was killed. Although the virB10 mutants are capable of short-term survival, they can not evade long-term degradation through fusion with lysosomes [Ref6547:Celli et al., 2003].
B abortus virB1 and virB10 mutants are unable to persist in mouse spleens after i.p. inoculation, suggest that attenuation in the animal model is due to an inability of these strains to grow intracellularly [Ref6463:Hong et al., 2000].
A B abortus virB10 mutant lost the ability to multiply in HeLa cells and was not recovered from the spleens of infected BALBc mice [Ref6538:Briones et al., 2001].
The non polar virB10 mutant was able to block the acquisition of cathepsin D, but was not able to translocate to the replication compartment [Ref6548:Boschiroli et al., 2002].
The virB10 non-polar mutants were capable of avoiding interactions with the endocytic pathway but , diverging to wild-type Brucella, were unable to reach the endoplasmic reticulum to establish their intracellular replication niche and seemed to be recycled to the cell surface [Ref6465:Comerci et al., 2001]. |
10940027
12925673
10858227
11401996
12414154
11260139
|
|
|
virb11 from Brucella melitensis bv. 1 str. 16M |
Brucella melitensis bv. 1 str. 16M |
1197806
|
|
17988379
|
BMEII0035 |
|
NP_541012.1 |
ATPASE VIRB11 HOMOLOG |
Virulence factor |
MUTATION: The virB11 mutation experiment confirms that a complete VirB apparatus is required for their secretion [Ref6464:Marchesini et al., 2004]. |
15312849
|
|
|
gltD |
Brucella melitensis bv. 1 str. 16M |
1197810
|
|
161511181
|
BMEII0039 |
AE008918 |
NP_541016 |
glutamate synthase subunit beta |
Virulence factor |
FUNCTIONAL GROUP: a.a. metabolism, Synthesis [Ref6462:Delrue et al., 2004].
FUNCTION: Glut. sunthesis [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Mice [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
gltD from Brucella melitensis bv. 1 str. 16M |
Brucella melitensis bv. 1 str. 16M |
1197811
|
|
17988384
|
BMEII0040 |
|
NP_541017.1 |
GLUTAMATE SYNTHASE [NADPH] LARGE CHAIN |
Virulence factor |
MUTATION: gltD encodes the small subunit of glutamate synthase. It is required for B. abortus growth as shown in signature-tagged transposon mutagenesis. It suggests that glutamate may serve as carbon and/or nitrogen sources during growth of B abortus [Ref6463:Hong et al., 2000]. |
10858227
|
|
|
nodV from Brucella melitensis bv. 1 str. 16M |
Brucella melitensis bv. 1 str. 16M |
1197823
|
|
17988396
|
BMEII0052 |
|
NP_541029.1 |
SENSORY TRANSDUCTION HISTIDINE KINASE |
Virulence factor |
FUNCTIONAL GROUP: Regulation [Ref6462:Delrue et al., 2004].
FUNCTION: Histidine kinase [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
mgtB from Brucella melitensis bv. 1 str. 16M |
Brucella melitensis bv. 1 str. 16M |
1197827
|
|
17988400
|
BMEII0056 |
|
NP_541033.1 |
MG(2+) TRANSPORT ATPASE, P-TYPE |
Virulence factor |
FUNCTIONAL GROUP: Metal acquisition [Ref6462:Delrue et al., 2004].
FUNCTION: Mg2+ uptake [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
dhbC |
Brucella melitensis bv. 1 str. 16M |
1197848
|
|
17988421
|
BMEII0077 |
AE008918 |
NP_541054 |
isochorismate synthase |
Virulence factor |
FUNCTIONAL GROUP: Metal acquisition [Ref6462:Delrue et al., 2004].
FUNCTION: Sideophore sysnhesis, Fe3+ uptake [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Pregant goat, but not in Mice, IFN-/-Mice, Macrophages, Trophoblastes [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
rbsK from Brucella melitensis bv. 1 str. 16M |
Brucella melitensis bv. 1 str. 16M |
1197860
|
|
17988433
|
BMEII0089 |
|
NP_541066.1 |
RIBOKINASE |
Virulence factor |
FUNCTIONAL GROUP: a.a. metabolism, Unkown [Ref6462:Delrue et al., 2004].
FUNCTION: Ribokinase [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Macrophages [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
gntR10 |
Brucella melitensis bv. 1 str. 16M |
1197887
|
|
17988460
|
BMEII0116 |
GG703779 |
NP_541093 |
GntR family transcriptional regulator |
Virulence factor |
FUNCTIONAL GROUP: gntR family [Ref6530:Haine et al., 2005].
MUTATION: Attenuated using plasmid-tagged mutagenesis method [Ref6530:Haine et al., 2005]. |
16113274
|
|
|
BMEII0128 |
Brucella |
1197899
|
|
17988472
|
BMEII0128 |
|
NP_541105.1 |
hypothetical protein |
Virulence factor |
FUNCTIONAL GROUP: Unkown function [Ref6462:Delrue et al., 2004].
FUNCTION: Uncharacterised protein family (DUF0261) [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
pheB |
Brucella melitensis bv. 1 str. 16M |
1197907
|
|
17988480
|
BMEII0136 |
AE008918 |
NP_541113 |
homoprotocatechuate 2,3-dioxygenase |
Virulence factor |
FUNCTIONAL GROUP: Other genes [Ref6462:Delrue et al., 2004].
FUNCTION: Dioxygenase [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Mice [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
fliC |
Brucella melitensis bv. 1 str. 16M |
1197921
|
|
17988494
|
BMEII0150 |
AE008918 |
NP_541127 |
flagellin |
Virulence factor |
FUNCTIONAL GROUP: "Classical virulence factors", Secretion of transport system, Flagella [Ref6462:Delrue et al., 2004].
FUNCTION: Flagellin [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Mice, but not in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
fliF from Brucella melitensis bv. 1 str. 16M |
Brucella melitensis bv. 1 str. 16M |
1197922
|
|
17988495
|
BMEII0151 |
|
NP_541128.1 |
FLAGELLAR M-RING PROTEIN FLIF |
Virulence factor |
FUNCTION: The M ring may be actively involved in energy transduction (By similarity)(Swiss-Prot: Q8FUS3).
SUBUNIT: The basal body constitutes a major portion of the flagellar organelle and consists of five rings (E,L,P,S, and M) mounted on a central rod. The M ring is integral to the inner membrane of the cell and may be connected to the flagellar rod via the S ring. The S (supramembrane ring) lies just distal to the M ring. The L and P rings lie in the outer membrane and the periplasmic space, respectively (By similarity)(Swiss-Prot: Q8FUS3).
SUBCELLULAR LOCATION: Inner membrane; multi-pass membrane protein (By similarity)(Swiss-Prot: Q8FUS3).
SIMILARITY: Belongs to the fliF family(Swiss-Prot: Q8FUS3).
MUTATION: fliF is a gene potentially coding for the MS ring, a basal component of the flagellar system. Its mutant through signature- tagged mutagenesis is attenuated in vivo. It implicate a role for flagella in virulenc [Ref6480:Lestrate et al., 2003]. |
14638795
|
|
|
motB from Brucella melitensis bv. 1 str. 16M |
Brucella melitensis bv. 1 str. 16M |
1197925
|
|
17988498
|
BMEII0154 |
|
NP_541131.1 |
flagellar motor protein MotB |
Virulence factor |
FUNCTIONAL GROUP: "Classical virulence factors", Secretion of transport system, Flagella [Ref6462:Delrue et al., 2004].
FUNCTION: Flagellar motor [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Mice, but not in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
ftcR |
Brucella melitensis bv. 1 str. 16M |
1197929
|
|
17988502
|
BMEII0158 |
NZ_GG703779 |
NP_541135 |
two component response regulator |
Virulence factor |
MUTATION: FtcR is required in B melitensis 16M for the transcription of the fliF gene during vegetative and intracellular growth, and for the production of the two structural flagellar components FlgE and FliC during vegetative growth. A ftcR mutant has the same virulence phenotype as previously found with structural flagellar mutants. In HeLa cells and bovine macrophages, no attenuation of the ftcR mutant was observed compared to the WT parental strain. In BALB/c mice, the ftcR mutant was not attenuated after 1 week of infection but was attenuated after 4 weeks of infection. FtcR acts as a flagellar master regulator in B melitensis and perhaps in other related alpha-proteobacteria [Ref6549:Léonard et al., 2007]. |
17056750
|
|
|
flgE from Brucella melitensis bv. 1 str. 16M |
Brucella melitensis bv. 1 str. 16M |
1197930
|
|
17988503
|
BMEII0159 |
|
NP_541136.1 |
flagellar hook protein FlgE |
Virulence factor |
FUNCTIONAL GROUP: "Classical virulence factors", Secretion of transport system, Flagella [Ref6462:Delrue et al., 2004].
FUNCTION: Hook [Ref6462:Delrue et al., 2004].
SIMILARITY: Belongs to the flagella basal body rod proteins family(Swiss-Prot: Q8FUS9).
MUTATION: Attenuated in Mice, but not in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
flghA |
Brucella melitensis bv. 1 str. 16M |
1197937
|
|
17988510
|
BMEII0166 |
AE008918 |
NP_541143 |
flagellar biosynthetic protein FlhA |
Virulence factor |
FUNCTIONAL GROUP: "Classical virulence factors", Secretion of transport system, Flagella [Ref6462:Delrue et al., 2004].
FUNCTION: Export apparatus [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Mice, but not in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
znuC from Brucella melitensis bv. 1 str. 16M |
Brucella melitensis bv. 1 str. 16M |
1197948
|
|
17988521
|
BMEII0177 |
|
NP_541154.1 |
HIGH-AFFINITY ZINC UPTAKE SYSTEM ATP-BINDING PROTEIN ZNUC |
Virulence factor |
FUNCTIONAL GROUP: Metal acquisition [Ref6462:Delrue et al., 2004].
FUNCTION: Zn2+ uptake [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
znuA from Brucella melitensis bv. 1 str. 16M |
Brucella melitensis bv. 1 str. 16M |
1197949
|
|
17988522
|
BMEII0178 |
AE008918 |
NP_541155 |
high-affinity zinc uptake system protein ZNUA |
Virulence factor |
MUTATION: Brucella abortus znuA mutant via mini-Tn5Km2 transposon mutagenesis has intracellular growth defect inside HeLa cells [Ref6469:Kim et al., 2003]. High-affinity zinc uptake system protein mutant (znuA mutant) showed reduced growth in zinc chelated medium, and failed to replicate in HeLa cells and mouse bone marrow-derived macrophages. Transformation of znuA mutant with a shuttle vector pBBR1MCS-4 containing znuA gene restored the growth in zinc chelated medium and intracellular replication in HeLa cells and macrophages to a level comparable to that of wild-type strain. Bacterial internalization into HeLa cells and macrophages and co-localization with either late endosomes or lysosomes of znuA mutant were not different from those of wild-type strain. These results suggest that znuA does not contribute to intracellular trafficking of B abortus, but contributes to utilization of zinc required for intracellular growth [Ref6550:Kim et al., 2004]. |
12761078
15472468
|
|
|
BMEII0274 |
Brucella |
1198045
|
|
17988618
|
BMEII0274 |
|
NP_541251.1 |
GTPase EngB |
Virulence factor |
FUNCTIONAL GROUP: Unkown function [Ref6462:Delrue et al., 2004].
FUNCTION: GTPase of unknown function domain, FeoB domain [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Macrophages [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
dbsA |
Brucella melitensis bv. 1 str. 16M |
1198072
|
|
17988645
|
BMEII0300 |
AE008918 |
NP_541278 |
ribose ABC transporter ATP-binding protein |
Virulence factor |
FUNCTIONAL GROUP: a.a. metabolism, Transport [Ref6462:Delrue et al., 2004].
FUNCTION: Ribose transport [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in HeLa [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
cobW from Brucella melitensis bv. 1 str. 16M |
Brucella melitensis bv. 1 str. 16M |
1198080
|
|
17988653
|
BMEII0308 |
|
NP_541286.1 |
LOW AFFINITY ZINC TRANSPORT MEMBRANE PROTEIN |
Virulence factor |
MUTATION: A study with miniTn5 mutants of B. suis constitutively expressing gfp indicates that B. suis cobW gene is required for intracellular multiplication in human macrophage THP-1 cells [Ref412:Kohler et al., 2002]. |
12438693
|
|
|
BMEII0318 |
Brucella |
1198090
|
|
17988663
|
BMEII0318 |
|
NP_541296.1 |
6-AMINOHEXANOATE-DIMER HYDROLASE |
Virulence factor |
FUNCTIONAL GROUP: Unkown function [Ref6462:Delrue et al., 2004].
FUNCTION: [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
BMEII0336 |
Brucella |
1198108
|
|
17988681
|
BMEII0336 |
|
NP_541314.1 |
ABC TRANSPORTER PERMEASE PROTEIN |
Virulence factor |
FUNCTIONAL GROUP: "Classical virulence factors", Secretion of transport system, Transpter [Ref6462:Delrue et al., 2004].
FUNCTION: ABC transporter [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
dacF from Brucella melitensis bv. 1 str. 16M |
Brucella melitensis bv. 1 str. 16M |
1198122
|
|
17988695
|
BMEII0350 |
|
NP_541328.1 |
D-aminopeptidase |
Virulence factor |
FUNCTIONAL GROUP: "Classical virulence factors", Envelope molecules, peptidoglycan [Ref6462:Delrue et al., 2004].
FUNCTION: Peptidoglycan synthesis [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
araG from Brucella melitensis bv. 1 str. 16M |
Brucella melitensis bv. 1 str. 16M |
1198133
|
|
17988706
|
BMEII0361 |
|
NP_541339.1 |
SUGAR TRANSPORT ATP-BINDING PROTEIN |
Virulence factor |
FUNCTIONAL GROUP: a.a. metabolism, Transport [Ref6462:Delrue et al., 2004].
FUNCTION: L-arabinose transport [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Differential fluorescence induction, but not in Macrophages [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
fdhA from Brucella melitensis bv. 1 str. 16M |
Brucella melitensis bv. 1 str. 16M |
1198150
|
|
17988723
|
BMEII0378 |
|
NP_541356.1 |
FORMATE DEHYDROGENASE ALPHA CHAIN |
Virulence factor |
FUNCTIONAL GROUP: Oxidoreduction [Ref6462:Delrue et al., 2004].
FUNCTION: Formate dehydrogenase [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Mice [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
lysR12 |
Brucella |
1198162
|
|
17988735
|
BMEII0390 |
|
NP_541368.1 |
TRANSCRIPTIONAL REGULATORY PROTEIN, LYSR FAMILY |
Virulence factor |
FUNCTIONAL GROUP: lysR family [Ref6530:Haine et al., 2005].
MUTATION: Attenuated using plasmid-tagged mutagenesis method [Ref6530:Haine et al., 2005]. |
16113274
|
|
|
eryC from Brucella melitensis bv. 1 str. 16M |
Brucella melitensis bv. 1 str. 16M |
1198200
|
|
17988773
|
BMEII0428 |
|
NP_541406.1 |
D-erythrulose 4-phosphate dehydrogenase |
Virulence factor |
MUTATION: The eryC gene encodes for enzyme Derythrulose-1-phosphate dehydrogenase. The vaccine strain B abortus B19 is the only known B abortus isolate whose growth is inhibited by erythritol. The B abortus B19 strain is an eryCD double mutant. The defect in B19 was complemented in trans by plasmids containing the complete ery region and by plasmids with Tn1725 insertions in eryA, eryB and eryD. Plasmids with Tn1725 insertions in eryC were the only ones that failed to complement the Ery phenotype of B19 [Ref6483:Sangari et al., 2000].
Allelic exchange mutants in eryC of Brucella suis were erythritol sensitive in vitro with a MIC of 1 to 5 mM of erythritol. Their multiplication in macrophage-like cells was 50 to 90- fold reduced , but complementation of the mutant restored wild-type levels of intracellular multiplication and the capacity to use erythritol as a sole carbon source. In vivo, the eryC mutant colonized the spleens of infected BALBc mice to a significantly lower extent than the wild type and the complemented strain. Interestingly, eryC mutants that were in addition spontaneously erythritol tolerant nevertheless exhibited wild-type-like intramacrophagic and intramurine replication. In conclusion, erythritol was not an essential carbon source for the pathogen in the macrophage host cell but that the inactivation of the eryC gene significantly reduced the intramacrophagic and intramurine fitness of B suis [Ref6551:Burkhardt et al., 2005]. |
10708387
16177356
|
|
|
eryB from Brucella melitensis bv. 1 str. 16M |
Brucella melitensis bv. 1 str. 16M |
1198201
|
|
17988774
|
BMEII0429 |
|
NP_541407.1 |
glycerol-3-phosphate dehydrogenase |
Virulence factor |
MUTATION: EryB is an erythritol phosphate dehydrogenase. The vaccine strain B abortus B19 is the only known B abortus isolate whose growth is inhibited by erythritol. The B abortus B19 strain is an eryCD double mutant. The defect in B19 was complemented in trans by plasmids containing the complete ery region and by plasmids with Tn1725 insertions in eryA, eryB and eryD. Plasmids with Tn1725 insertions in eryC were the only ones that failed to complement the Ery phenotype of B19 [Ref6483:Sangari et al., 2000].
The B. suis eryB mutant by Tn5 transposon mutagenesis was attenuated in the human macrophage -like THP-1 cells. This mutant is sensitive to erythritol and mimics the erythritol sensitive response of the B19 strain [Ref6551:Burkhardt et al., 2005]. |
10708387
16177356
|
|
|
gntR1 |
Brucella melitensis bv. 1 str. 16M |
1198247
|
|
17988820
|
BMEII0475 |
AE008918 |
NP_541453 |
GntR family transcriptional regulator |
Virulence factor |
FUNCTIONAL GROUP: gntR family [Ref6530:Haine et al., 2005].
MUTATION: Attenuated using plasmid-tagged mutagenesis method [Ref6530:Haine et al., 2005]. |
16113274
|
|
|
galcD from Brucella melitensis bv. 1 str. 16M |
Brucella melitensis bv. 1 str. 16M |
1198257
|
|
17988830
|
BMEII0485 |
|
NP_541463.1 |
D-GALACTARATE DEHYDRATASE |
Virulence factor |
FUNCTIONAL GROUP: a.a. metabolism, Unkown [Ref6462:Delrue et al., 2004].
FUNCTION: D-galactarate dehydratase [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
nikA from Brucella melitensis bv. 1 str. 16M |
Brucella melitensis bv. 1 str. 16M |
1198259
|
|
17988832
|
BMEII0487 |
|
NP_541465.1 |
NICKEL-BINDING PERIPLASMIC PROTEIN PRECURSOR |
Virulence factor |
FUNCTIONAL GROUP: Metal acquisition [Ref6462:Delrue et al., 2004].
FUNCTION: Ni2+ uptake [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Differential fluorescence induction, but not in Macrophages, Mice [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
zwf from Brucella melitensis bv. 1 str. 16M |
Brucella melitensis bv. 1 str. 16M |
1198285
|
|
17988858
|
BMEII0513 |
|
NP_541491.1 |
glucose-6-phosphate 1-dehydrogenase |
Virulence factor |
MUTATION: Brucella abortus zwf mutant via mini-Tn5Km2 transposon mutagenesis has intracellular growth defect inside HeLa cells and macrophages [Ref6469:Kim et al., 2003]. |
12761078
|
|
|
xseA from Brucella melitensis bv. 1 str. 16M |
Brucella melitensis bv. 1 str. 16M |
1198299
|
|
17988872
|
BMEII0527 |
|
NP_541505.1 |
exodeoxyribonuclease VII large subunit |
Virulence factor |
FUNCTION: Bidirectionally degrades single-stranded DNA into large acid-insoluble oligonucleotides, which are then degraded further into small acid-soluble oligonucleotides (By similarity)(Swiss-Prot: Q8FVR1).
CATALYTIC ACTIVITY: Exonucleolytic cleavage in either 5'- to 3'- or 3'- to 5'-direction to yield nucleoside 5'-phosphates(Swiss-Prot: Q8FVR1).
SUBUNIT: Heterooligomer composed of large and small subunits (By similarity)(Swiss-Prot: Q8FVR1).
SUBCELLULAR LOCATION: Cytoplasm (By similarity)(Swiss-Prot: Q8FVR1).
SIMILARITY: Belongs to the xseA family(Swiss-Prot: Q8FVR1).
MUTATION: xseA codes for an exodeoxyribonuclease. B. melitensis xseA mutant via signature-tagged mutagenesis is attenuated in vivo in mice [Ref6480:Lestrate et al., 2003]. |
14638795
|
|
|
mocC from Brucella melitensis bv. 1 str. 16M |
Brucella melitensis bv. 1 str. 16M |
1198342
|
|
17988915
|
BMEII0570 |
|
NP_541548.1 |
IOLE PROTEIN |
Virulence factor |
FUNCTIONAL GROUP: a.a. metabolism, Unkown [Ref6462:Delrue et al., 2004].
FUNCTION: Rhizopine/inositol catabolism [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Differential fluorescence induction, Mice, but not in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
RpiR from Brucella melitensis bv. 1 str. 16M |
Brucella melitensis bv. 1 str. 16M |
1198345
|
|
17988918
|
BMEII0573 |
|
NP_541551.1 |
TRANSCRIPTIONAL REGULATOR, RPIR FAMILY |
Virulence factor |
FUNCTIONAL GROUP: Regulation [Ref6462:Delrue et al., 2004].
FUNCTION: Transcriptional regulator [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Mice, but not in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
sodC from Brucella melitensis bv. 1 str. 16M |
Brucella melitensis bv. 1 str. 16M |
1198353
|
|
17988926
|
BMEII0581 |
|
NP_541559.1 |
SUPEROXIDE DISMUTASE (CU-ZN) |
Virulence factor |
FUNCTION: Destroys radicals which are normally produced within the cells and which are toxic to biological systems (By similarity)(Swiss-Prot: P66827).
CATALYTIC ACTIVITY: 2 superoxide + 2 H(+) = O(2) + H(2)O(2)(Swiss-Prot: P66827).
COFACTOR: Binds 1 copper ion per subunit (By similarity)(Swiss-Prot: P66827).
COFACTOR: Binds 1 zinc ion per subunit (By similarity)(Swiss-Prot: P66827).
SUBUNIT: Homodimer (By similarity)(Swiss-Prot: P66827).
SUBCELLULAR LOCATION: Periplasmic (By similarity)(Swiss-Prot: P66827).
SIMILARITY: Belongs to the Cu-Zn superoxide dismutase family(Swiss-Prot: P66827).
IMMUNOGENICITY: Induces antigen-specific Th1 immune response, as indicated by the specific induction of serum IgG2a, but not IgG1, antibodies and by the secretion of IFN-γ, but not IL-4, by the Cu/Zn SOD-stimulated splenocytes. Has been used for vaccine development [Ref6552:Vemulapalli et al., 2000][Ref6552:Vemulapalli et al., 2000][Ref6552:Vemulapalli et al., 2000].
MUTATION: An isogenic sodC mutant constructed from B abortus 2308 by gene replacement exhibited much greater susceptibility to killing by exogenous O(2)(-) than the parental 2308 strain, supporting a role for SodC in protecting this bacterium from O(2)(-) stress. The B abortus sodC mutant was much more sensitive to killing by cultured resident peritoneal macrophages from C57BL6J mice than 2308, and its attenuation in cultured murine macrophages was enhanced when these phagocytes were treated with gamma interferon. The attenuation of the B abortus sodC mutant in both resting and IFN-gamma -activated macrophages was alleviated in the presence of the NADPH oxidase inhibitor apocynin. Consistently, the B abortus sodC mutant also displayed significant attenuation in infected C57BL6J mice compared to the parental strain. These findings suggest that SodC protects B abortus 2308 from the respiratory burst of host macrophages [Ref6552:Vemulapalli et al., 2000]. |
10816475
|
|
|
fbpA from Brucella melitensis bv. 1 str. 16M |
Brucella melitensis bv. 1 str. 16M |
1198356
|
|
17988929
|
BMEII0584 |
|
NP_541562.1 |
IRON(III)-BINDING PERIPLASMIC PROTEIN PRECURSOR |
Virulence factor |
FUNCTIONAL GROUP: Metal acquisition [Ref6462:Delrue et al., 2004].
FUNCTION: Fe3+ binding [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Differential fluorescence induction [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
ugpA from Brucella melitensis bv. 1 str. 16M |
Brucella melitensis bv. 1 str. 16M |
1198363
|
|
17988936
|
BMEII0591 |
|
NP_541569.1 |
SUGAR TRANSPORT SYSTEM PERMEASE PROTEIN |
Virulence factor |
MUTATION: UgpA is one of the attenuated Signature-Tagged Mutagenesis mutants of Brucella melitensis identified during the acute phase of infection in mice [Ref6480:Lestrate et al., 2003]. |
14638795
|
|
|
ugpA from Brucella melitensis bv. 1 str. 16M |
Brucella melitensis bv. 1 str. 16M |
1198396
|
|
17988969
|
BMEII0624 |
|
NP_541602.1 |
SN-GLYCEROL-3-PHOSPHATE TRANSPORT SYSTEM PERMEASE PROTEIN UGPA |
Virulence factor |
MUTATION: UgpA is one of the attenuated Signature-Tagged Mutagenesis mutants of Brucella melitensis identified during the acute phase of infection in mice [Ref6480:Lestrate et al., 2003]. |
14638795
|
|
|
BMEII0626 |
Brucella |
1198398
|
|
17988971
|
BMEII0626 |
|
NP_541604.1 |
MEMBRANE DIPEPTIDASE |
Virulence factor |
FUNCTIONAL GROUP: Unkown function [Ref6462:Delrue et al., 2004].
FUNCTION: Dipeptidase domain [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
divK from Brucella melitensis bv. 1 str. 16M |
Brucella melitensis bv. 1 str. 16M |
1198431
|
|
17989004
|
BMEII0659 |
|
NP_541637.1 |
TWO COMPONENT RESPONSE REGULATOR |
Virulence factor |
FUNCTIONAL GROUP: Regulation [Ref6462:Delrue et al., 2004].
FUNCTION: Response regulator [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Mice [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
pyrC from Brucella melitensis bv. 1 str. 16M |
Brucella melitensis bv. 1 str. 16M |
1198441
|
|
17989014
|
BMEII0669 |
|
NP_541647.1 |
dihydroorotase |
Virulence factor |
FUNCTIONAL GROUP: DNA/RNA metabolism, Synthesis [Ref6462:Delrue et al., 2004].
FUNCTION: dihydroorotase [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
pyrB from Brucella melitensis bv. 1 str. 16M |
Brucella melitensis bv. 1 str. 16M |
1198442
|
|
17989015
|
BMEII0670 |
|
NP_541648.1 |
aspartate carbamoyltransferase catalytic subunit |
Virulence factor |
CATALYTIC ACTIVITY: Carbamoyl phosphate + L-aspartate = phosphate + N-carbamoyl-L-aspartate(Swiss-Prot: P65612).
PATHWAY: Nucleotide biosynthesis; UMP biosynthesis; UMP from HCO(3)(-): step 2(Swiss-Prot: P65612).
PATHWAY: Context: Pyrimidine biosynthesis(Swiss-Prot: P65612).
SIMILARITY: Belongs to the ATCase/OTCase family(Swiss-Prot: P65612).
MUTATION: B. abortus pyrB (pyrimidines) gene is essential for intracellular growth in HeLa cells as shown from transposon mutagenesis study [Ref6469:Kim et al., 2003]. |
12761078
|
|
|
aidB from Brucella melitensis bv. 1 str. 16M |
Brucella melitensis bv. 1 str. 16M |
1198443
|
|
17989016
|
BMEII0671 |
|
NP_541649.1 |
ACYL-COA DEHYDROGENASE |
Virulence factor |
FUNCTIONAL GROUP: DNA/RNA metabolism, Repair [Ref6462:Delrue et al., 2004].
FUNCTION: Protection against alkylation damage to DNA [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Macrophages [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
rbsC from Brucella melitensis bv. 1 str. 16M |
Brucella melitensis bv. 1 str. 16M |
1198473
|
|
17989046
|
BMEII0701 |
|
NP_541679.1 |
RIBOSE TRANSPORT SYSTEM PERMEASE PROTEIN RBSC |
Virulence factor |
FUNCTIONAL GROUP: "Classical virulence factors", Secretion of transport system, Transpter [Ref6462:Delrue et al., 2004].
FUNCTION: ABC transporter [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
cydB from Brucella melitensis bv. 1 str. 16M |
Brucella melitensis bv. 1 str. 16M |
1198531
|
|
17989104
|
BMEII0759 |
|
NP_541737.1 |
CYTOCHROME D UBIQUINOL OXIDASE SUBUNIT II |
Virulence factor |
MUTATION: cydB is a gene that is part of the cydAB operon encoding cytochrome bd oxidase , which catalyzes an alternate terminal electron transport step in bacterial respiration. Transposon (Tn5) mutagenesis of B abortus cydB was severely attenuated for intracellular survival. Unlike the virulent strain 2308, the Brucella cydB::Tn5 mutant was severely compromised for survival in the spleens of inoculated mice [Ref6477:Endley et al., 2001]. The cydB and cydD mutants are also defective for the intracellular growth of B abortus and B suis, suggesting that functional cytochrome bd oxidase is required for growth in an intracellular environment [Ref6469:Kim et al., 2003]. |
11274104
12761078
|
|
|
cydC from Brucella melitensis bv. 1 str. 16M |
Brucella melitensis bv. 1 str. 16M |
1198533
|
|
17989106
|
BMEII0761 |
|
NP_541739.1 |
TRANSPORT ATP-BINDING PROTEIN CYDC |
Virulence factor |
FUNCTIONAL GROUP: Oxidoreduction [Ref6462:Delrue et al., 2004].
FUNCTION: Cytochrome oxidase [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
cydD from Brucella melitensis bv. 1 str. 16M |
Brucella melitensis bv. 1 str. 16M |
1198534
|
|
17989107
|
BMEII0762 |
|
NP_541740.1 |
TRANSPORT ATP-BINDING PROTEIN CYDD |
Virulence factor |
MUTATION: The cydB and cydD mutants are also defective for the intracellular growth of B abortus and B suis, suggesting that functional cytochrome bd oxidase is required for growth in an intracellular environment [Ref6469:Kim et al., 2003]. |
12761078
|
|
|
ssuB from Brucella melitensis bv. 1 str. 16M |
Brucella melitensis bv. 1 str. 16M |
1198571
|
|
17989144
|
BMEII0799 |
|
NP_541777.1 |
NITRATE TRANSPORT PERMEASE PROTEIN NRTB |
Virulence factor |
FUNCTIONAL GROUP: "Classical virulence factors", Secretion of transport system, Transpter [Ref6462:Delrue et al., 2004].
FUNCTION: Permease [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Differential fluorescence induction [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
glpK from Brucella melitensis bv. 1 str. 16M |
Brucella melitensis bv. 1 str. 16M |
1198595
|
|
17989168
|
BMEII0823 |
|
NP_541801.1 |
GLYCEROL KINASE |
Virulence factor |
FUNCTION: Key enzyme in the regulation of glycerol uptake and metabolism(Swiss-Prot: Q8FWK8).
CATALYTIC ACTIVITY: ATP + glycerol = ADP + sn-glycerol 3-phosphate(Swiss-Prot: Q8FWK8).
PATHWAY: Glycerol utilization; first (rate-limiting) step(Swiss-Prot: Q8FWK8).
SIMILARITY: Belongs to the FGGY kinase family(Swiss-Prot: Q8FWK8).
MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
xfp from Brucella melitensis bv. 1 str. 16M |
Brucella melitensis bv. 1 str. 16M |
1198653
|
|
17989226
|
BMEII0881 |
|
NP_541859.1 |
putative phosphoketolase |
Virulence factor |
FUNCTIONAL GROUP: a.a. metabolism, Degradation [Ref6462:Delrue et al., 2004].
FUNCTION: Lys. degradation [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
manB from Brucella melitensis bv. 1 str. 16M |
Brucella melitensis bv. 1 str. 16M |
1198671
|
|
17989244
|
BMEII0899 |
|
NP_541877.1 |
PHOSPHOMANNOMUTASE |
Virulence factor |
FUNCTIONAL GROUP: "Classical virulence factors", Envelope molecules, Lipopolysaccharide [Ref6462:Delrue et al., 2004].
FUNCTION: O-chain biosynthesis [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
wbpW from Brucella melitensis bv. 1 str. 16M |
Brucella melitensis bv. 1 str. 16M |
1198672
|
|
17989245
|
BMEII0900 |
|
NP_541878.1 |
MANNOSE-6-PHOSPHATE ISOMERASE / MANNOSE-1-PHOSPHATE GUANYLYL TRANSFERASE (GDP) |
Virulence factor |
FUNCTIONAL GROUP: "Classical virulence factors", Envelope molecules, Lipopolysaccharide [Ref6462:Delrue et al., 2004].
FUNCTION: O-chain biosynthesis [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Macrophages [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
BMEII0923 |
Brucella |
1198695
|
|
17989268
|
BMEII0923 |
|
NP_541901.1 |
SPERMIDINE/PUTRESCINE-BINDING PERIPLASMIC PROTEIN |
Virulence factor |
FUNCTIONAL GROUP: "Classical virulence factors", Secretion of transport system, Transpter [Ref6462:Delrue et al., 2004].
FUNCTION: ABC transporter [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Mice [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
nrdI |
Brucella melitensis bv. 1 str. 16M |
1198703
|
|
17989276
|
BMEII0931 |
GG703779 |
NP_541909 |
ribonucleotide reductase stimulatory protein |
Virulence factor |
FUNCTIONAL GROUP: DNA/RNA metabolism, Synthesis [Ref6462:Delrue et al., 2004].
FUNCTION: Ribonucleotide recuctase [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Differential fluorescence induction, HeLa, but not in Macrophages [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
nrdH from Brucella melitensis bv. 1 str. 16M |
Brucella melitensis bv. 1 str. 16M |
1198704
|
|
17989277
|
BMEII0932 |
|
NP_541910.1 |
GLUTAREDOXIN |
Virulence factor |
FUNCTIONAL GROUP: DNA/RNA metabolism, Synthesis [Ref6462:Delrue et al., 2004].
FUNCTION: Ribonucleotide recuctase [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in HeLa, but not in Macrophages, mice [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
BMEII0935 |
Brucella |
1198707
|
|
17989280
|
BMEII0935 |
|
NP_541913.1 |
NICKEL RESISTANCE PROTEIN |
Virulence factor |
FUNCTIONAL GROUP: Unkown function [Ref6462:Delrue et al., 2004].
FUNCTION: Bacterial protein of unknown function (DUF89) [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
narG from Brucella melitensis bv. 1 str. 16M |
Brucella melitensis bv. 1 str. 16M |
1198722
|
|
17989295
|
BMEII0950 |
|
NP_541928.1 |
NITRATE REDUCTASE ALPHA CHAIN |
Virulence factor |
MUTATION: The narG gene encodes for an essential component of the dissimilatory nitrate reductase complex. This complex is encoded by the narGHIJ locus, which is present in the B suis genome together with the gene of the nitrite extrusion protein, narK. The narG mutant was unable to produce nitrite from nitrate [Ref412:Kohler et al., 2002]. A study with miniTn5 mutants of B. suis constitutively expressing gfp indicates that B. suis xx gene is required for intracellular multiplication in human macrophage THP-1 cells [Ref412:Kohler et al., 2002]. |
12438693
|
|
|
norE from Brucella melitensis bv. 1 str. 16M |
Brucella melitensis bv. 1 str. 16M |
1198773
|
|
17989346
|
BMEII1001 |
|
NP_541979.1 |
NORE PROTEIN |
Virulence factor |
FUNCTIONAL GROUP: Oxidoreduction [Ref6462:Delrue et al., 2004].
FUNCTION: Nitric oxide reduction [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Mice, but not in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
BMEII1037 |
Brucella |
1198809
|
|
17989382
|
BMEII1037 |
|
NP_542015.1 |
ZINC PROTEASE |
Virulence factor |
FUNCTIONAL GROUP: Other genes [Ref6462:Delrue et al., 2004].
FUNCTION: Zinc protease [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Mice [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
BMEII1045 |
Brucella |
1198817
|
|
17989390
|
BMEII1045 |
|
NP_542023.1 |
HAD superfamily protein involved in N-acetyl-glucosamine catabolism |
Virulence factor |
FUNCTIONAL GROUP: Unkown function [Ref6462:Delrue et al., 2004].
FUNCTION: haloacid dehalogenase-like hydrolase domain [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
gluP from Brucella melitensis bv. 1 str. 16M |
Brucella melitensis bv. 1 str. 16M |
1198825
|
|
17989398
|
BMEII1053 |
|
NP_542031.1 |
GLUCOSE/GALACTOSE TRANSPORTER |
Virulence factor |
FUNCTION: Intake of glucose and galactose (Potential)(Swiss-Prot: Q8YB48).
SUBCELLULAR LOCATION: Inner membrane; multi-pass membrane protein (Probable)(Swiss-Prot: Q8YB48).
SIMILARITY: Belongs to the major facilitator superfamily. FHS transporter (TC 2.A.1.7) family(Swiss-Prot: Q8YB48).
MUTATION: B suis and maybe B canis seem to have two glucosegalactose transporters: gluP and gguAB. B abortus may express only gluP, which may explain why gluP mutants fail to survive long periods in the mouse [Ref6474:Essenberg et al., 2002]. |
12414147
|
|
|
gntR from Brucella melitensis bv. 1 str. 16M |
Brucella melitensis bv. 1 str. 16M |
1198838
|
|
17989411
|
BMEII1066 |
|
NP_542044.1 |
PYRUVATE DEHYDROGENASE COMPLEX REPRESSOR |
Virulence factor |
FUNCTIONAL GROUP: Regulation [Ref6462:Delrue et al., 2004].
FUNCTION: Transcriptional regulator [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
flgI from Brucella melitensis bv. 1 str. 16M |
Brucella melitensis bv. 1 str. 16M |
1198856
|
|
17989429
|
BMEII1084 |
|
NP_542062.1 |
flagellar basal body P-ring protein |
Virulence factor |
FUNCTIONAL GROUP: "Classical virulence factors", Secretion of transport system, Flagella [Ref6462:Delrue et al., 2004].
FUNCTION: P-ring [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Mice, but not in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
deoR from Brucella melitensis bv. 1 str. 16M |
Brucella melitensis bv. 1 str. 16M |
1198865
|
|
17989438
|
BMEII1093 |
|
NP_542071.1 |
GLYCEROL-3-PHOSPHATE REGULON REPRESSOR |
Virulence factor |
FUNCTIONAL GROUP: Regulation [Ref6462:Delrue et al., 2004].
FUNCTION: Transcriptional regulator [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Macrophages [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
gtrB from Brucella melitensis bv. 1 str. 16M |
Brucella melitensis bv. 1 str. 16M |
1198873
|
|
17989446
|
BMEII1101 |
|
NP_542079.1 |
BACTOPRENOL GLUCOSYL TRANSFERASE / BACTOPRENOL APOLIPOPROTEIN N-ACYLTRANSFERASE |
Virulence factor |
FUNCTIONAL GROUP: a.a. metabolism, Unkown [Ref6462:Delrue et al., 2004].
FUNCTION: glycosyl transerase [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Macrophages [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
vjbR from Brucella melitensis bv. 1 str. 16M |
Brucella melitensis bv. 1 str. 16M |
1198888
|
|
17989461
|
BMEII1116 |
|
NP_542094.1 |
TRANSCRIPTIONAL ACTIVATOR, LUXR FAMILY |
Virulence factor |
FUNCTIONAL GROUP: Regulation [Ref6462:Delrue et al., 2004].
FUNCTION: Transcriptional regulator [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
gnd from Brucella melitensis bv. 1 str. 16M |
Brucella melitensis bv. 1 str. 16M |
1198896
|
|
17989469
|
BMEII1124 |
|
NP_542102.1 |
6-phosphogluconate dehydrogenase |
Virulence factor |
MUTATION: gnd is involved in pentose phosphate pathway. It is essential for intracellular growth inside HeLa cells as shown by its Brucella suis miniTn5Km2 transposon mutation analysis. The mutant is attenuated in the mouse model [Ref6469:Kim et al., 2003]. |
12761078
|
|
|
metH from Brucella melitensis biovar Abortus 2308 |
Brucella melitensis biovar Abortus 2308 |
3786978
|
|
82699102
|
BAB1_0188 |
|
YP_413676.1 |
B12-dependent methionine synthase |
Virulence factor |
FUNCTIONAL GROUP: a.a. metabolism, Synthesis [Ref6462:Delrue et al., 2004].
FUNCTION: Met. synthesis [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
pgi from Brucella melitensis biovar Abortus 2308 |
Brucella melitensis biovar Abortus 2308 |
3787092
|
|
82699210
|
BAB1_0316 |
|
YP_413784.1 |
glucose-6-phosphate isomerase |
Virulence factor |
CATALYTIC ACTIVITY: D-glucose 6-phosphate = D-fructose 6-phosphate(Swiss-Prot: Q8G2N3).
PATHWAY: Carbohydrate degradation; glycolysis; D-glyceraldehyde 3-phosphate and glycerone phosphate from D-glucose: step 2(Swiss-Prot: Q8G2N3).
SUBCELLULAR LOCATION: Cytoplasm (By similarity)(Swiss-Prot: Q8G2N3).
SIMILARITY: Belongs to the GPI family(Swiss-Prot: Q8G2N3).
MUTATION: B. suis pgi is a gene identified by signature-tagged mutagenesis. The mutant is attenuated inside THP1 macrophages. The mutation of the pgi gene could also affect the biosynthesis of the bacterial peptidoglycan [Ref6484:Foulongne et al., 2000]. |
10678941
|
|
|
tig from Brucella melitensis biovar Abortus 2308 |
Brucella melitensis biovar Abortus 2308 |
3787589
|
|
82699768
|
BAB1_0917 |
|
YP_414342.1 |
trigger factor |
Virulence factor |
FUNCTION: Involved in protein export. Acts as a chaperone by maintaining the newly synthesized protein in an open conformation (By similarity)(Swiss-Prot: Q8G129).
SIMILARITY: Belongs to the FKBP-type PPIase family. Tig subfamily(Swiss-Prot: Q8G129).
SIMILARITY: Contains 1 PPIase FKBP-type domain(Swiss-Prot: Q8G129).
MUTATION: tig encodes for Trigger factor that helps protein folding and secretion. It is one of the attenuated Signature-Tagged Mutagenesis mutants of Brucella melitensis identified during the acute phase of infection in mice [Ref6480:Lestrate et al., 2003]. |
14638795
|
|
|
uvrA from Brucella melitensis biovar Abortus 2308 |
Brucella melitensis biovar Abortus 2308 |
3787776
|
|
82699947
|
BAB1_1128 |
|
YP_414521.1 |
excinuclease ABC subunit A |
Virulence factor |
FUNCTION: The UvrABC repair system catalyzes the recognition and processing of DNA lesions. UvrA is an ATPase and a DNA-binding protein. A damage recognition complex composed of 2 uvrA and 2 uvrB subunits scans DNA for abnormalities. When the presence of a lesion has been verified by uvrB, the uvrA molecules dissociate (By similarity)(Swiss-Prot: Q8G0I9).
SUBUNIT: Forms a heterotetramer with uvrB during the search for lesions (By similarity)(Swiss-Prot: Q8G0I9).
SUBCELLULAR LOCATION: Cytoplasm (By similarity)(Swiss-Prot: Q8G0I9).
SIMILARITY: Belongs to the ABC transporter family. UvrA subfamily(Swiss-Prot: Q8G0I9).
SIMILARITY: Contains 2 ABC transporter domains(Swiss-Prot: Q8G0I9).
MUTATION: B. abortus urvA and recA mutants exhibited greater sensitivity than the wild-type strain. Mutant strains carrying inactivated uvrA genes are typically less sensitive than recA mutants because there is only the loss of the nucleotide excision repair system, just one subset of the larger repair networks. However, it was found that the recA mutant conferred only a modest sensitivity to UV, substantially less sensitive than the uvrA mutant. High basal recA expression was observed in the uvrA repair mutant. The B abortus recA mutant exhibited a nearly fourfold decline in survival to murine peritoneal macrophages but nominal sensitivity for the uvrA and radA repair mutants [Ref6493:Roux et al., 2006]. |
16816190
|
|
|
miaA from Brucella melitensis biovar Abortus 2308 |
Brucella melitensis biovar Abortus 2308 |
3787973
|
|
82700207
|
BAB1_1409 |
|
YP_414781.1 |
tRNA delta(2)-isopentenylpyrophosphate transferase |
Virulence factor |
FUNCTION: Catalyzes the first step in the biosynthesis of 2-methylthio-N6-(delta(2)-isopentenyl)-adenosine (MS[2]I[6]A) adjacent to the anticodon of several tRNA species (By similarity)(Swiss-Prot: Q8CY40).
CATALYTIC ACTIVITY: Isopentenyl diphosphate + tRNA = diphosphate + tRNA containing 6-isopentenyladenosine(Swiss-Prot: Q8CY40).
SIMILARITY: Belongs to the IPP transferase family(Swiss-Prot: Q8CY40).
MUTATION: A study with miniTn5 mutants of B. suis constitutively expressing gfp indicates that B. suis miaA gene is required for intracellular multiplication in human macrophage THP-1 cells [Ref412:Kohler et al., 2002]. |
12438693
|
|
|
aroC from Brucella melitensis biovar Abortus 2308 |
Brucella melitensis biovar Abortus 2308 |
3788622
|
|
82699340
|
BAB1_0454 |
|
YP_413914.1 |
chorismate synthase |
Virulence factor |
CATALYTIC ACTIVITY: 5-O-(1-carboxyvinyl)-3-phosphoshikimate = chorismate + phosphate(Swiss-Prot: P63608).
COFACTOR: Reduced flavin (By similarity)(Swiss-Prot: P63608).
PATHWAY: Metabolic intermediate biosynthesis; chorismate biosynthesis; chorismate from D-erythrose 4-phosphate and PEP: step 7 [final step](Swiss-Prot: P63608).
PATHWAY: Context: Aromatic amino acids biosynthesis(Swiss-Prot: P63608).
SUBUNIT: Homotetramer (By similarity)(Swiss-Prot: P63608).
SIMILARITY: Belongs to the chorismate synthase family(Swiss-Prot: P63608).
MUTATION: The cloned aroC gene complements Escherichia coli and Salmonella enterica serovar Typhimurium aroC mutants. A B suis aroC mutant was found to be unable to grow in a defined medium without aromatic compounds. The mutant was highly attenuated in it issue culture (THP1 macrophages and HeLa cells) and murine virulence models [Ref6488:Foulongne et al., 2001]. |
11119550
|
|
|
aspC from Brucella melitensis biovar Abortus 2308 |
Brucella melitensis biovar Abortus 2308 |
3788626
|
|
82700306
|
BAB1_1514 |
|
YP_414880.1 |
aspartate aminotransferase |
Virulence factor |
MUTATION: aspC encodes for an aminotransferase. B.abortus aspC mutant obtained from randomized miniTn5Km2 transposon mutagenesis showed decreased intracellular survival inside HeLa cells. So B. abortus aspC gene is essential for HeLa cell intracellular growth [Ref6469:Kim et al., 2003]. |
12761078
|
|
|
bacA from Brucella melitensis biovar Abortus 2308 |
Brucella melitensis biovar Abortus 2308 |
3788635
|
|
82699288
|
BAB1_0402 |
|
YP_413862.1 |
transport protein |
Virulence factor |
MUTATION: B abortus bacA mutant exhibited decreased survival in macrophages and greatly accelerated clearance from experimentally infected mice compared to the virulent parental strain [Ref6487:LeVier et al., 2000]. R meliloti bacA gene encodes a putative cytoplasmic membrane transport protein required for symbiosis [Ref6487:LeVier et al., 2000]. The BacA protein is essential for the long-term survival of Sinorhizobium meliloti and Brucella abortus within acidic compartments in plant and animal cells , respectively. Mutation study showed that B. abortus BacA affects the distribution of LPS fatty acids, including a very-long-chain fatty acid thought to be unique to the alpha-proteobacteria[Ref6487:LeVier et al., 2000]. |
10741969
|
|
|
cysI from Brucella melitensis biovar Abortus 2308 |
Brucella melitensis biovar Abortus 2308 |
3788677
|
|
82699095
|
BAB1_0181 |
|
YP_413669.1 |
Nitrite/sulfite reductase ferredoxin-like half domain:Nitrite and sulfite reductase iron-sulfur/siroheme-binding site:Nitrite... |
Virulence factor |
FUNCTIONAL GROUP: Oxidoreduction [Ref6462:Delrue et al., 2004].
FUNCTION: Sulfite reductate [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Mice, Macrophages, but not in HeLa [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
dut from Brucella melitensis biovar Abortus 2308 |
Brucella melitensis biovar Abortus 2308 |
3788687
|
|
82700463
|
BAB1_1687 |
|
YP_415037.1 |
deoxyuridine 5'-triphosphate nucleotidohydrolase |
Virulence factor |
FUNCTION: This enzyme is involved in nucleotide metabolism: it produces dUMP, the immediate precursor of thymidine nucleotides and it decreases the intracellular concentration of dUTP so that uracil cannot be incorporated into DNA (By similarity)(Swiss-Prot: P64005).
CATALYTIC ACTIVITY: dUTP + H(2)O = dUMP + diphosphate(Swiss-Prot: P64005).
PATHWAY: De novo synthesis of thymidylate(Swiss-Prot: P64005).
SIMILARITY: Belongs toMUTATION: A study with miniTn5 mutants of B. suis constitutively expressing gfp indicates that B. suis dut gene is required for intracellular multiplication in human macrophage THP-1 cells [Ref412:Kohler et al., 2002]. the dUTPase family(Swiss-Prot: P64005). |
12438693
|
|
|
glnA from Brucella melitensis biovar Abortus 2308 |
Brucella melitensis biovar Abortus 2308 |
3788725
|
|
82699855
|
BAB1_1023 |
|
YP_414429.1 |
Glutamine synthetase class-I, adenylation site:Glutamine synthetase type I:Glutamine synthetase, catalytic domain:Glutamine s... |
Virulence factor |
MUTATION: A study with miniTn5 mutants of B. suis constitutively expressing gfp indicates that B. suis glnA gene is required for intracellular multiplication in human macrophage THP-1 cells [Ref412:Kohler et al., 2002]. |
12438693
|
|
|
gloA from Brucella melitensis biovar Abortus 2308 |
Brucella melitensis biovar Abortus 2308 |
3788728
|
|
82700098
|
BAB1_1286 |
|
YP_414672.1 |
Glyoxalase/Bleomycin resistance protein/dioxygenase domain:Glyoxalase I |
Virulence factor |
FUNCTIONAL GROUP: a.a. metabolism, Unkown [Ref6462:Delrue et al., 2004].
FUNCTION: Lactoylglutathione lyase (pyruvate metabolism) [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Differential fluorescence induction [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
glyA from Brucella melitensis biovar Abortus 2308 |
Brucella melitensis biovar Abortus 2308 |
3788734
|
|
82699646
|
BAB1_0787 |
|
YP_414220.1 |
serine hydroxymethyltransferase |
Virulence factor |
FUNCTION: Interconversion of serine and glycine(Swiss-Prot: Q8G1F1).
CATALYTIC ACTIVITY: 5,10-methylenetetrahydrofolate + glycine + H(2)O = tetrahydrofolate + L-serine(Swiss-Prot: Q8G1F1).
COFACTOR: Pyridoxal phosphate (By similarity)(Swiss-Prot: Q8G1F1).
PATHWAY: Key enzyme in the biosynthesis of purines, lipids, hormones and other components(Swiss-Prot: Q8G1F1).
SUBUNIT: Homotetramer (By similarity)(Swiss-Prot: Q8G1F1).
SUBCELLULAR LOCATION: Cytoplasm (By similarity)(Swiss-Prot: Q8G1F1).
SIMILARITY: Belongs to the SHMT family(Swiss-Prot: Q8G1F1).
MUTATION: A study with miniTn5 mutants of B. suis constitutively expressing gfp indicates that B. suis glyA gene is required for intracellular multiplication in human macrophage THP-1 cells [Ref412:Kohler et al., 2002]. |
12438693
|
|
|
gmd from Brucella melitensis biovar Abortus 2308 |
Brucella melitensis biovar Abortus 2308 |
3788735
|
|
82699425
|
BAB1_0545 |
|
YP_413999.1 |
Short-chain dehydrogenase/reductase SDR:GDP-mannose 4,6-dehydratase |
Virulence factor |
MUTATION: gmd may be involved in perosamine synthesis. It has been shown to be in LPS synthesis since its B. melitensis mutation induces rough phenotype [Ref6490:Moriyón et al., 2004]. |
15099501
|
|
|
hfq from Brucella melitensis biovar Abortus 2308 |
Brucella melitensis biovar Abortus 2308 |
3788748
|
|
82699953
|
BAB1_1134 |
|
YP_414527.1 |
RNA-binding protein Hfq |
Virulence factor |
FUNCTION: RNA-binding protein that stimulates the elongation of poly(A) tails (By similarity)(Swiss-Prot: P0A3G8).
SIMILARITY: Belongs to the hfq family(Swiss-Prot: P0A3G8).
MUTATION: hfq encodes for the RNA binding protein host factor I (HF-I). The hfq knock out strain has been showed a reduced growth rate and is unable to utilize glucose as a sole carbon source[Ref6495:Sonnleitner et al., 2003].
hfq is required for the efficient translation of the stationary-phase sigma factor RpoS in many bacteria, and a Brucella abortus hfq mutant displays a phenotype in vitro, which suggests that it has a generalized defect in stationary-phase physiology. The inability of the B. abortus hfq mutant to survive and replicate in a wild-type manner in cultured murine macrophages, and the profound attenuation displayed by this strain and its B melitensis counterpart in experimentally infected animals indicate that stationary -phase physiology plays an essential role in the capacity of the brucellae to establish and maintain long-term intracellular residence in host macrophages [Ref6532:Roop et al., 2003].
In contrast to B abortus 2308, the isogenic hfq and bacA mutants remained in acidic, LAMP-1 phagosomes and failed to initiate intracellular replication [Ref6532:Roop et al., 2003].
A hfq mutant of B abortus was eliminated from mouse spleens more rapidly than the wild type [Ref6532:Roop et al., 2003]. |
14521880
12730323
|
|
|
hisC from Brucella melitensis biovar Abortus 2308 |
Brucella melitensis biovar Abortus 2308 |
3788751
|
|
82700747
|
BAB1_1988 |
|
YP_415321.1 |
histidinol-phosphate aminotransferase |
Virulence factor |
CATALYTIC ACTIVITY: L-histidinol phosphate + 2-oxoglutarate = 3-(imidazol-4-yl)-2-oxopropyl phosphate + L-glutamate(Swiss-Prot: Q8FY98).
COFACTOR: Pyridoxal phosphate (By similarity)(Swiss-Prot: Q8FY98).
PATHWAY: Amino-acid biosynthesis; L-histidine biosynthesis; L-histidine from 5-phospho-alpha-D-ribose 1-diphosphate: step 7(Swiss-Prot: Q8FY98).
SUBUNIT: Homodimer (By similarity)(Swiss-Prot: Q8FY98).
SIMILARITY: Belongs to the class-II pyridoxal-phosphate-dependent aminotransferase family. Histidinol-phosphate aminotransferase subfamily(Swiss-Prot: Q8FY98).
MUTATION: hisC encodes for histidinol phosphate transaminase. Brucella hisC mutant showed very little reduction in number by 2 weeks post-inoculation, but was reduced by 8 weeks. |
|
|
|
hisD |
Brucella |
3788752
|
|
82699185
|
BAB1_0285 |
|
YP_413759.1 |
histidinol dehydrogenase |
Virulence factor |
FUNCTION: Catalyzes the sequential NAD-dependent oxidations of L-histidinol to L-histidinaldehyde and then to L-histidine (By similarity)(Swiss-Prot: Q8G2R2).
CATALYTIC ACTIVITY: L-histidinol + 2 NAD(+) = L-histidine + 2 NADH(Swiss-Prot: Q8G2R2).
COFACTOR: Binds 1 zinc ion per subunit (By similarity)(Swiss-Prot: Q8G2R2).
PATHWAY: Amino-acid biosynthesis; L-histidine biosynthesis; L-histidine from 5-phospho-alpha-D-ribose 1-diphosphate: step 9 [final step](Swiss-Prot: Q8G2R2).
SIMILARITY: Belongs to the histidinol dehydrogenase family(Swiss-Prot: Q8G2R2).
MUTATION: A study with miniTn5 mutants of B. suis constitutively expressing gfp indicates that B. suis hisD gene is required for intracellular multiplication in human macrophage THP-1 cells [Ref412:Kohler et al., 2002]. |
12438693
|
|
|
hisF from Brucella melitensis biovar Abortus 2308 |
Brucella melitensis biovar Abortus 2308 |
3788754
|
|
82700840
|
BAB1_2086 |
|
YP_415414.1 |
imidazole glycerol phosphate synthase subunit HisF |
Virulence factor |
FUNCTION: IGPS catalyzes the conversion of PRFAR and glutamine to IGP, AICAR and glutamate. The hisF subunit catalyzes the cyclization activity that produces IGP and AICAR from PRFAR using the ammonia provided by the hisH subunit (By similarity)(Swiss-Prot: Q8FY07).
CATALYTIC ACTIVITY: 5-[(5-phospho-1-deoxyribulos-1-ylamino)methylideneamino]-1-(5-phosphoribosyl)imidazole-4-carboxamide + L-glutamine = imidazole-glycerol phosphate + 5-aminoimidazol-4-carboxamide ribonucleotide + L-glutamate + H(2)O(Swiss-Prot: Q8FY07).
PATHWAY: Amino-acid biosynthesis; L-histidine biosynthesis; L-histidine from 5-phospho-alpha-D-ribose 1-diphosphate: step 5(Swiss-Prot: Q8FY07).
SUBUNIT: Heterodimer of hisH and hisF (By similarity)(Swiss-Prot: Q8FY07).
SUBCELLULAR LOCATION: Cytoplasm (By similarity)(Swiss-Prot: Q8FY07).
SIMILARITY: Belongs to the hisA/hisF family(Swiss-Prot: Q8FY07).
MUTATION: A study with miniTn5 mutants of B. suis constitutively expressing gfp indicates that B. suis hisF gene is required for intracellular multiplication in human macrophage THP-1 cells [Ref412:Kohler et al., 2002]. |
12438693
|
|
|
hpt from Brucella melitensis biovar Abortus 2308 |
Brucella melitensis biovar Abortus 2308 |
3788755
|
|
82700745
|
BAB1_1986 |
|
YP_415319.1 |
Phosphoribosyltransferase:Hypoxanthine phosphoribosyl transferase |
Virulence factor |
FUNCTIONAL GROUP: DNA/RNA metabolism, Synthesis [Ref6462:Delrue et al., 2004].
FUNCTION: Purines synthesis [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
ilvD from Brucella melitensis biovar Abortus 2308 |
Brucella melitensis biovar Abortus 2308 |
3788763
|
|
82699018
|
BAB1_0096 |
|
YP_413592.1 |
dihydroxy-acid dehydratase |
Virulence factor |
CATALYTIC ACTIVITY: 2,3-dihydroxy-3-methylbutanoate = 3-methyl-2-oxobutanoate + H(2)O(Swiss-Prot: Q8G353).
COFACTOR: Binds 1 4Fe-4S cluster (Potential)(Swiss-Prot: Q8G353).
PATHWAY: Amino-acid biosynthesis; L-isoleucine biosynthesis; L-isoleucine from 2-oxobutanoate: step 3(Swiss-Prot: Q8G353).
PATHWAY: Amino-acid biosynthesis; L-valine biosynthesis; L-valine from pyruvate: step 3(Swiss-Prot: Q8G353).
SIMILARITY: Belongs to the ilvD/edd family(Swiss-Prot: Q8G353).
MUTATION: Of those B abortus mutants with mini-Tn5 insertions in genes predicted to be involved in amino acid biosynthesis and transport, only the ilvD mutant, displayed attenuation in both macrophages and mice. The othre two amino acid biosynthesis mutants [trpB::miniTn5 and pheA::miniTn5] displayed wild-type virulence in mice but attenuated inside macrophages. The studies with B abortus ilvD, trpB, and pheA mutants suggest that tryptophan and phenylalanine are available to the brucellae in their intracellular niche but that other amino acids (eg, leucine, isoleucine, or valine) are not [Ref6485:Alcantara et al., 2004]. |
15271960
|
|
|
leuA from Brucella melitensis biovar Abortus 2308 |
Brucella melitensis biovar Abortus 2308 |
3788771
|
|
162002872
|
BAB1_1583 |
|
YP_414947.2 |
2-isopropylmalate synthase |
Virulence factor |
FUNCTION: Catalyzes the condensation of the acetyl group of acetyl-CoA with 3-methyl-2-oxobutanoate (2-oxoisovalerate) to form 3-carboxy-3-hydroxy-4-methylpentanoate (2-isopropylmalate)(Swiss-Prot: Q8FZC4).
CATALYTIC ACTIVITY: Acetyl-CoA + 3-methyl-2-oxobutanoate + H(2)O = (2S)-2-isopropylmalate + CoA(Swiss-Prot: Q8FZC4).
PATHWAY: Amino-acid biosynthesis; L-leucine biosynthesis; L-leucine from 3-methyl-2-oxobutanoate: step 1(Swiss-Prot: Q8FZC4).
SUBUNIT: Homotetramer (By similarity)(Swiss-Prot: Q8FZC4).
SIMILARITY: Belongs to the alpha-IPM synthetase/homocitrate synthase family. LeuA type 2 subfamily(Swiss-Prot: Q8FZC4).
MUTATION: leuA is a B. suis gene identified by signature-tagged mutagenesis. It is attenuated inside THP1 macrophage cell line. |
|
|
|
leuC from Brucella melitensis biovar Abortus 2308 |
Brucella melitensis biovar Abortus 2308 |
3788772
|
|
82700673
|
BAB1_1905 |
|
YP_415247.1 |
isopropylmalate isomerase large subunit |
Virulence factor |
FUNCTION: Catalyzes the isomerization between 2-isopropylmalate and 3-isopropylmalate, via the formation of 2-isopropylmaleate(Swiss-Prot: Q8FYG9).
CATALYTIC ACTIVITY: (2R,3S)-3-isopropylmalate = (2S)-2-isopropylmaleate + H(2)O(Swiss-Prot: Q8FYG9).
CATALYTIC ACTIVITY: (2S)-2-isopropylmaleate + H(2)O = 3-hydroxy-4-methyl-3-carboxypentanoate(Swiss-Prot: Q8FYG9).
COFACTOR: Binds 1 4Fe-4S cluster per subunit (By similarity)(Swiss-Prot: Q8FYG9).
PATHWAY: Amino-acid biosynthesis; L-leucine biosynthesis; L-leucine from 3-methyl-2-oxobutanoate: step 2(Swiss-Prot: Q8FYG9).
SUBUNIT: Heterodimer of leuC and leuD (By similarity)(Swiss-Prot: Q8FYG9).
SIMILARITY: Belongs to the aconitase/IPM isomerase family. LeuC type 1 subfamily(Swiss-Prot: Q8FYG9).
MUTATION: A study with miniTn5 mutants of B. suis constitutively expressing gfp indicates that B. suis leuC gene is required for intracellular multiplication in human macrophage THP-1 cells [Ref412:Kohler et al., 2002]. |
12438693
|
|
|
lysA from Brucella melitensis biovar Abortus 2308 |
Brucella melitensis biovar Abortus 2308 |
3788788
|
|
82700743
|
BAB1_1984 |
|
YP_415317.1 |
Orn/DAP/Arg decarboxylase, family 2:ATP/GTP-binding site motif A (P-loop):Diaminopimelate decarboxylase |
Virulence factor |
MUTATION: A study with miniTn5 mutants of B. suis constitutively expressing gfp indicates that B. suis lysA gene is required for intracellular multiplication in human macrophage THP-1 cells [Ref412:Kohler et al., 2002]. |
12438693
|
|
|
ntrC from Brucella melitensis biovar Abortus 2308 |
Brucella melitensis biovar Abortus 2308 |
3788817
|
|
82699958
|
BAB1_1140 |
|
YP_414532.1 |
CbxX/CfqX superfamily:Response regulator receiver:Sigma-54 factor interaction domain:Helix-turn-helix, Fis-type:AAA ATPase |
Virulence factor |
MUTATION: ntrC encodes for a response regulator subfamily (NtrC). A B suis ntrC isogenic mutant was constructed which showed no significant differences in growth rates compared to the wild-type strain when grown at different temperatures in vitro. However, the mutant exhibited a reduction in metabolic activity in the presence of many amino acids. The mutation did not affect survival or multiplication of B suis in macrophages, but during the initial stages of infection in the murine brucellosis model, the ntrC mutant showed a reduced ability to multiply rapidly in splenic tissue [Ref6496:Dorrell et al., 1999]. |
10373105
|
|
|
ntrY from Brucella melitensis biovar Abortus 2308 |
Brucella melitensis biovar Abortus 2308 |
3788818
|
|
82699957
|
BAB1_1139 |
|
YP_414531.1 |
PAS domain:ATP-binding region, ATPase-like:Histidine kinase, HAMP region:Histidine kinase A, N-terminal:Bacterial sensor prot... |
Virulence factor |
MUTATION: The NtrY protein is a sensor of an ntr-related regulon which may be part of the glnALG operon. This mutant has a weakly attenuated phenotype (reduction of 1.2 log units versus the wild type at 48 h postinfection) which could be explained by a pleiotropic effect on the ntr regulon, since the ntrC mutant did not show such a phenotype [Ref6484:Foulongne et al., 2000]. |
10678941
|
|
|
omp19 from Brucella melitensis biovar Abortus 2308 |
Brucella melitensis biovar Abortus 2308 |
3788831
|
|
82700695
|
BAB1_1930 |
|
YP_415269.1 |
lipoprotein Omp19 |
Virulence factor |
SUBCELLULAR LOCATION: Outer membrane; lipid-anchor(Swiss-Prot: P0A3P2).
MISCELLANEOUS: Elicits an immune response in humans, mice, sheep and goats infected with B.melitensis or B.abortus, but not in B.abortus-infected cattle(Swiss-Prot: P0A3P2).
SIMILARITY: Belongs to the rhizobiaceae omp19 lipoprotein family(Swiss-Prot: P0A3P2).
MUTATION: Omp19 is an immunoreactive outer membrane lipoprotein. Significantly fewer brucellae were recovered from the spleens of mice infected with the omp19 mutant than from those of mice infected with the parent strain at 4 and 8 weeks postinfection. The omp19 mutant exhibited an increase in sensitivity to the polycation polymyxin B and to sodium deoxycholate. These results indicate that inactivation of the omp19 gene alters the outer membrane properties of B abortus [Ref6473:Tibor et al., 2002]. |
12228280
|
|
|
pepN from Brucella melitensis biovar Abortus 2308 |
Brucella melitensis biovar Abortus 2308 |
3788843
|
|
82699509
|
BAB1_0641 |
|
YP_414083.1 |
Membrane alanine aminopeptidase:Neutral zinc metallopeptidase, zinc-binding region |
Virulence factor |
MUTATION: A single mutation of PepN leads to a significant decrease in the growth rate, thus PepN seems to play a more prominent role than do the other proteases [Ref6491:Contreras-Rodriguez et al., 2003]. |
12933870
|
|
|
pgm from Brucella melitensis biovar Abortus 2308 |
Brucella melitensis biovar Abortus 2308 |
3788847
|
|
82698981
|
BAB1_0055 |
|
YP_413555.1 |
phosphoglucomutase |
Virulence factor |
MUTATION: Brucella pgm encodes the phosphoglucomutase. The B. abortus pgm mutant (B2211) lacks the O antigen. However, the core region of the mutant LPS migrated in Tricine-PAGE electrophoresis in a position that was indistinguishable from that of the wild type core. Although the exponential intracellular replication of the pgm mutant was delayed by approximately 20 h with respect to that of the wild type, the high number of recoverable bacteria at 48 h postinfection indicates that mutant strain B2211 replicates inside HeLa host cells [Ref6486:Ugalde et al., 2000].
B abortus phosphoglucomutase (pgm) insertional mutants were attenuated in vivo but not in vitro [Ref6486:Ugalde et al., 2000]. |
10992476
|
|
|
pheA from Brucella melitensis biovar Abortus 2308 |
Brucella melitensis biovar Abortus 2308 |
3788850
|
|
82698963
|
BAB1_0034 |
|
YP_413537.1 |
prephenate dehydratase |
Virulence factor |
MUTATION: The product of pheA gene is specifically dedicated to the biosynthesis of phenylalanine. The B. abortus pheA mutant with mini-Tn5 disruption displays nutritional defects in vitro. Experimental findings with the B abortus ilvD, trpB, and pheA mutants suggest that tryptophan and phenylalanine are available to the brucellae in their intracellular niche but that other amino acids (eg, leucine, isoleucine, or valine) are not. The pheA::miniTn5 mutant displayed attenuation in macrophages but not in mice [Ref6485:Alcantara et al., 2004]. |
15271960
|
|
|
pth from Brucella melitensis biovar Abortus 2308 |
Brucella melitensis biovar Abortus 2308 |
3788869
|
|
82700344
|
BAB1_1552 |
|
YP_414918.1 |
peptidyl-tRNA hydrolase |
Virulence factor |
FUNCTION: The natural substrate for this enzyme may be peptidyl-tRNAs which drop off the ribosome during protein synthesis (By similarity)(Swiss-Prot: P65864).
CATALYTIC ACTIVITY: N-substituted aminoacyl-tRNA + H(2)O = N-substituted amino acid + tRNA(Swiss-Prot: P65864).
SUBUNIT: Monomer (By similarity)(Swiss-Prot: P65864).
SUBCELLULAR LOCATION: Cytoplasm (By similarity)(Swiss-Prot: P65864).
SIMILARITY: Belongs to the PTH family(Swiss-Prot: P65864).
MUTATION: pth encodes for a peptidyl tRNA hydrolase. Transposon insertion in pth has a polar effect on dugA expression and that the pth/dugA mutant is deficient in iron assimilation because of altered expression of the dugA gene. Only minor difference in intracellular growth in bovine macrophages and HeLa cells between the pth/dugA mutant and wild-type strains was observed [Ref6498:Danese et al., 2004]. |
15385478
|
|
|
purD from Brucella melitensis biovar Abortus 2308 |
Brucella melitensis biovar Abortus 2308 |
3788874
|
|
82699328
|
BAB1_0442 |
|
YP_413902.1 |
phosphoribosylamine--glycine ligase |
Virulence factor |
CATALYTIC ACTIVITY: ATP + 5-phospho-D-ribosylamine + glycine = ADP + phosphate + N(1)-(5-phospho-D-ribosyl)glycinamide(Swiss-Prot: Q8G2B1).
PATHWAY: Nucleotide biosynthesis; IMP biosynthesis; N(1)-(5-phospho-D-ribosyl)glycinamide from 5-phospho-alpha-D-ribose 1-diphosphate: step 2(Swiss-Prot: Q8G2B1).
PATHWAY: Context: Purine biosynthesis(Swiss-Prot: Q8G2B1).
SIMILARITY: Belongs to the GARS family(Swiss-Prot: Q8G2B1).
SIMILARITY: Contains 1 ATP-grasp domain(Swiss-Prot: Q8G2B1).
MUTATION: Brucella abortus 2308 derivatives with mini-Tn5 insertions in purE, purL, and purD display significant attenuation in the BALBc mouse model. It confirms the importance of the purine biosynthesis pathways for the survival and replication of the brucellae in host macrophages [Ref6595:Drazek et al., 1995].
Like the purE mutant, a purD::Tn10 mutant has reduced survival in murine macrophages and reduced virulence in mice [Ref6595:Drazek et al., 1995]. |
7642258
|
|
|
purF from Brucella melitensis biovar Abortus 2308 |
Brucella melitensis biovar Abortus 2308 |
3788875
|
|
82699358
|
BAB1_0472 |
|
YP_413932.1 |
amidophosphoribosyltransferase |
Virulence factor |
MUTATION: A B. suis purF mutation experiment suggests that the purine biosynthesis pathway contributes to intracellular growth [Ref6469:Kim et al., 2003]. |
12761078
|
|
|
purH from Brucella melitensis biovar Abortus 2308 |
Brucella melitensis biovar Abortus 2308 |
3788876
|
|
82700596
|
BAB1_1824 |
|
YP_415170.1 |
bifunctional phosphoribosylaminoimidazolecarboxamide formyltransferase/IMP cyclohydrolase |
Virulence factor |
CATALYTIC ACTIVITY: 10-formyltetrahydrofolate + 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide = tetrahydrofolate + 5-formamido-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide(Swiss-Prot: P67540).
CATALYTIC ACTIVITY: IMP + H(2)O = 5-formamido-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide(Swiss-Prot: P67540).
PATHWAY: Nucleotide biosynthesis; IMP biosynthesis; 5-formamido-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide from 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide (10-formyl THF route): single step(Swiss-Prot: P67540).
PATHWAY: Nucleotide biosynthesis; IMP biosynthesis; IMP from 5-formamido-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide: single step [final step](Swiss-Prot: P67540).
PATHWAY: Context: Purine biosynthesis(Swiss-Prot: P67540).
DOMAIN: The IMP cyclohydrolase activity resides in the N-terminal region (By similarity)(Swiss-Prot: P67540).
SIMILARITY: Belongs to the purH family(Swiss-Prot: P67540).
MUTATION: B. abortus mutant with mini-Tn5-disrupted purH displays nutritional defects in vitro [Ref6485:Alcantara et al., 2004]. |
15271960
|
|
|
purM from Brucella melitensis biovar Abortus 2308 |
Brucella melitensis biovar Abortus 2308 |
3788878
|
|
82699599
|
BAB1_0731 |
|
YP_414173.1 |
phosphoribosylaminoimidazole synthetase |
Virulence factor |
CATALYTIC ACTIVITY: ATP + 2-(formamido)-N(1)-(5-phospho-D-ribosyl)acetamidine = ADP + phosphate + 5-amino-1-(5-phospho-D-ribosyl)imidazole(Swiss-Prot: Q8G1K5).
PATHWAY: Nucleotide biosynthesis; IMP biosynthesis; 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide from N(2)-formyl-N(1)-(5-phospho-D-ribosyl)glycinamide: step 2(Swiss-Prot: Q8G1K5).
PATHWAY: Context: Purine biosynthesis(Swiss-Prot: Q8G1K5).
SUBCELLULAR LOCATION: Cytoplasm (By similarity)(Swiss-Prot: Q8G1K5).
SIMILARITY: Belongs to the AIR synthase family(Swiss-Prot: Q8G1K5).
MUTATION: B. abortus purM gene is essential for intracellular growth in HeLa cells as shown from transposon mutagenesis study [Ref6469:Kim et al., 2003]. |
12761078
|
|
|
purN from Brucella melitensis biovar Abortus 2308 |
Brucella melitensis biovar Abortus 2308 |
3788879
|
|
162002876
|
BAB1_0730 |
|
YP_414172.2 |
phosphoribosylglycinamide formyltransferase |
Virulence factor |
MUTATION: B. abortus purN gene is essential for intracellular growth in HeLa cells as shown from transposon mutagenesis study [Ref6469:Kim et al., 2003]. |
12761078
|
|
|
pyc from Brucella melitensis biovar Abortus 2308 |
Brucella melitensis biovar Abortus 2308 |
3788880
|
|
82700564
|
BAB1_1791 |
|
YP_415138.1 |
pyruvate carboxylase |
Virulence factor |
MUTATION: pyc is one B. suis gene identified by signature-tagged mutagenesis. It is essential for survival and mulitplication in macrophages [Ref6484:Foulongne et al., 2000]. |
10678941
|
|
|
pyrD from Brucella melitensis biovar Abortus 2308 |
Brucella melitensis biovar Abortus 2308 |
3788883
|
|
82699235
|
BAB1_0341 |
|
YP_413809.1 |
dihydroorotate dehydrogenase 2 |
Virulence factor |
MUTATION: B. suis pyrD mutation study indicated that pyrimidine synthesis pathway contributes to intracellular growth [Ref6469:Kim et al., 2003]. |
12761078
|
|
|
recA from Brucella melitensis biovar Abortus 2308 |
Brucella melitensis biovar Abortus 2308 |
3788897
|
|
82700036
|
BAB1_1224 |
|
YP_414610.1 |
recombinase A |
Virulence factor |
FUNCTION: Can catalyze the hydrolysis of ATP in the presence of single-stranded DNA, the ATP-dependent uptake of single-stranded DNA by duplex DNA, and the ATP-dependent hybridization of homologous single-stranded DNAs. It interacts with lexA causing its activation and leading to its autocatalytic cleavage (By similarity)(Swiss-Prot: P65976).
SUBCELLULAR LOCATION: Cytoplasm (By similarity)(Swiss-Prot: P65976).
SIMILARITY: Belongs to the recA family(Swiss-Prot: P65976).
MUTATION: The RecA mutant was more sensitive than the parental strain to killing by MMS. When administered intraperitoneally to BALBc mice, numbers of bacteria per spleen were consistently lower in animals infected with the RecA mutant than with the parental strain. However, both the RecA mutant and parental strain persisted in mice through 100 days post-infection. These results indicate that RecA is not crucial for persistence of B abortus in mice [Ref6531:Tatum et al., 1993].
The B abortus RecA mutant was virulent in mice, but its course of infection in mice differed from that of the parental strain. The infectious cycle of the parental strain in the mouse model was biphasic. During the rst week, there was an initial rise in cfu of B abortus 2308 in the spleen followed by a decrease during the second week. This phase was followed by a second phase in which B abortus S2308 persisted and slowly increased in numbers in the spleen . Though fewer RecA mutants were found in the spleens of mice infected intraperitoneally in the early stages of the infection and no large initial rise was seen, the same numbers were found as the parental strain 100 days post -infection. This suggests that collectively, different loci are involved to varying extents in the initial infection and the persistence phase [Ref6531:Tatum et al., 1993].
|
8321120
|
|
|
rfbD from Brucella melitensis biovar Abortus 2308 |
Brucella melitensis biovar Abortus 2308 |
3788901
|
|
82699423
|
BAB1_0543 |
|
YP_413997.1 |
ABC transporter, family 2:Acriflavin resistance protein |
Virulence factor |
FUNCTIONAL GROUP: "Classical virulence factors", Envelope molecules, Lipopolysaccharide [Ref6462:Delrue et al., 2004].
FUNCTION: O-chain biosynthesis [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Mice, Macrophages [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
rplS from Brucella melitensis biovar Abortus 2308 |
Brucella melitensis biovar Abortus 2308 |
3788922
|
|
82700674
|
BAB1_1906 |
|
YP_415248.1 |
50S ribosomal protein L19 |
Virulence factor |
FUNCTION: This protein is located at the 30S-50S ribosomal subunit interface and may play a role in the structure and function of the aminoacyl-tRNA binding site (By similarity)(Swiss-Prot: P66079).
SIMILARITY: Belongs to the ribosomal protein L19P family(Swiss-Prot: P66079).
MUTATION: rplS is involved in traanslation. B. abortus rplS mutant by the mini-Tn5 disruption displays nutritional defects in vitro [Ref6485:Alcantara et al., 2004]. |
15271960
|
|
|
rpoA from Brucella melitensis biovar Abortus 2308 |
Brucella melitensis biovar Abortus 2308 |
3788935
|
|
82700043
|
BAB1_1231 |
|
YP_414617.1 |
DNA-directed RNA polymerase subunit alpha |
Virulence factor |
FUNCTION: DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates(Swiss-Prot: Q8G094).
CATALYTIC ACTIVITY: Nucleoside triphosphate + RNA(n) = diphosphate + RNA(n+1)(Swiss-Prot: Q8G094).
SUBUNIT: Homodimer. The RNAP catalytic core consists of 2 alpha, 1 beta, 1 beta' and 1 omega subunit. When a sigma factor is associated with the core the holoenzyme is formed, which can initiate transcription (By similarity)(Swiss-Prot: Q8G094).
DOMAIN: The N-terminal domain is essential for RNAP assembly and basal transcription, whereas the C-terminal domain is involved in interaction with transcriptional regulators and with upstream promoter elements (By similarity)(Swiss-Prot: Q8G094).
SIMILARITY: Belongs to the RNA polymerase alpha chain family(Swiss-Prot: Q8G094).
MUTATION: The rpoA gene codes for the essential alpha-subunit of the RNA polymerase. B. melitensis rpoA mutant was found by signature-tagged mutagenesis from a mouse infection model. This disruption leaves a partially functional protein, impaired for the activation of virB transcription, as demonstrated by the absence of induction of the virB promoter in the Tn5::rpoA background. RpoA is involved in virB regulation in vitro. The mutant (Tn5::rpoA) was more resistant to oxidative stress [Ref6480:Lestrate et al., 2003]. |
14638795
|
|
|
rpsA from Brucella melitensis biovar Abortus 2308 |
Brucella melitensis biovar Abortus 2308 |
3788939
|
|
82698954
|
BAB1_0025 |
|
YP_413528.1 |
30S ribosomal protein S1 |
Virulence factor |
MUTATION: rpsA is a B. suis gene identified by signature-tagged mutagenesis [Ref6484:Foulongne et al., 2000]. |
10678941
|
|
|
flgE from Brucella melitensis biovar Abortus 2308 |
Brucella melitensis biovar Abortus 2308 |
3827409
|
|
83269934
|
BAB2_1098 |
|
YP_419225.1 |
flagellar hook protein FlgE |
Virulence factor |
FUNCTIONAL GROUP: "Classical virulence factors", Secretion of transport system, Flagella [Ref6462:Delrue et al., 2004].
FUNCTION: Hook [Ref6462:Delrue et al., 2004].
SIMILARITY: Belongs to the flagella basal body rod proteins family(Swiss-Prot: Q8FUS9).
MUTATION: Attenuated in Mice, but not in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
motB from Brucella melitensis biovar Abortus 2308 |
Brucella melitensis biovar Abortus 2308 |
3827414
|
|
83269939
|
BAB2_1103 |
|
YP_419230.1 |
flagellar motor protein MotB |
Virulence factor |
FUNCTIONAL GROUP: "Classical virulence factors", Secretion of transport system, Flagella [Ref6462:Delrue et al., 2004].
FUNCTION: Flagellar motor [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Mice, but not in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
ugpA from Brucella melitensis biovar Abortus 2308 |
Brucella melitensis biovar Abortus 2308 |
3827693
|
|
83269477
|
BAB2_0584 |
|
YP_418768.1 |
Binding-protein-dependent transport systems inner membrane component:Blood group Rhesus C/E and D polypeptide |
Virulence factor |
MUTATION: UgpA is one of the attenuated Signature-Tagged Mutagenesis mutants of Brucella melitensis identified during the acute phase of infection in mice [Ref6480:Lestrate et al., 2003]. |
14638795
|
|
|
ugpB from Brucella melitensis biovar Abortus 2308 |
Brucella melitensis biovar Abortus 2308 |
3827694
|
|
83269478
|
BAB2_0585 |
|
YP_418769.1 |
Bacterial extracellular solute-binding protein, family 1 |
Virulence factor |
MUTATION: B suis ugpB mutant does not contain SP41 protein. Mutants lacking SP41 production are less invasive, but proliferate in HeLa cells. An isogenic DeltaugpB mutant showed a significant inhibitory effect on Brucella adherence and invasion of human cultured epithelial cells and this effect could be reversed by restoration of the ugpB on a plasmid. [Ref6479:Castañeda-Roldán et al., 2006]. |
16817909
|
|
|
znuA from Brucella melitensis biovar Abortus 2308 |
Brucella melitensis biovar Abortus 2308 |
3827700
|
|
83269918
|
BAB2_1079 |
|
YP_419209.1 |
Periplasmic solute binding protein |
Virulence factor |
MUTATION: Brucella abortus znuA mutant via mini-Tn5Km2 transposon mutagenesis has intracellular growth defect inside HeLa cells [Ref6469:Kim et al., 2003]. High-affinity zinc uptake system protein mutant (znuA mutant) showed reduced growth in zinc chelated medium, and failed to replicate in HeLa cells and mouse bone marrow-derived macrophages. Transformation of znuA mutant with a shuttle vector pBBR1MCS-4 containing znuA gene restored the growth in zinc chelated medium and intracellular replication in HeLa cells and macrophages to a level comparable to that of wild-type strain. Bacterial internalization into HeLa cells and macrophages and co-localization with either late endosomes or lysosomes of znuA mutant were not different from those of wild-type strain. These results suggest that znuA does not contribute to intracellular trafficking of B abortus, but contributes to utilization of zinc required for intracellular growth [Ref6469:Kim et al., 2003]. |
12761078
|
|
|
znuC from Brucella melitensis biovar Abortus 2308 |
Brucella melitensis biovar Abortus 2308 |
3827702
|
|
83269919
|
BAB2_1080 |
|
YP_419210.1 |
ATP/GTP-binding site motif A (P-loop):ABC transporter:AAA ATPase |
Virulence factor |
FUNCTIONAL GROUP: Metal acquisition [Ref6462:Delrue et al., 2004].
FUNCTION: Zn2+ uptake [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
nrdH from Brucella melitensis biovar Abortus 2308 |
Brucella melitensis biovar Abortus 2308 |
3827703
|
|
83269752
|
BAB2_0891 |
|
YP_419043.1 |
Glutaredoxin |
Virulence factor |
FUNCTIONAL GROUP: DNA/RNA metabolism, Synthesis [Ref6462:Delrue et al., 2004].
FUNCTION: Ribonucleotide recuctase [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in HeLa, but not in Macrophages, mice [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
pyrB from Brucella melitensis biovar Abortus 2308 |
Brucella melitensis biovar Abortus 2308 |
3827823
|
|
83269525
|
BAB2_0641 |
|
YP_418816.1 |
aspartate carbamoyltransferase catalytic subunit |
Virulence factor |
CATALYTIC ACTIVITY: Carbamoyl phosphate + L-aspartate = phosphate + N-carbamoyl-L-aspartate(Swiss-Prot: P65612).
PATHWAY: Nucleotide biosynthesis; UMP biosynthesis; UMP from HCO(3)(-): step 2(Swiss-Prot: P65612).
PATHWAY: Context: Pyrimidine biosynthesis(Swiss-Prot: P65612).
SIMILARITY: Belongs to the ATCase/OTCase family(Swiss-Prot: P65612).
MUTATION: B. abortus pyrB (pyrimidines) gene is essential for intracellular growth in HeLa cells as shown from transposon mutagenesis study [Ref6469:Kim et al., 2003]. |
12761078
|
|
|
sodC from Brucella melitensis biovar Abortus 2308 |
Brucella melitensis biovar Abortus 2308 |
3827840
|
|
83269434
|
BAB2_0535 |
|
YP_418725.1 |
Copper/Zinc superoxide dismutase |
Virulence factor |
FUNCTION: Destroys radicals which are normally produced within the cells and which are toxic to biological systems (By similarity)(Swiss-Prot: P66827).
CATALYTIC ACTIVITY: 2 superoxide + 2 H(+) = O(2) + H(2)O(2)(Swiss-Prot: P66827).
COFACTOR: Binds 1 copper ion per subunit (By similarity)(Swiss-Prot: P66827).
COFACTOR: Binds 1 zinc ion per subunit (By similarity)(Swiss-Prot: P66827).
SUBUNIT: Homodimer (By similarity)(Swiss-Prot: P66827).
SUBCELLULAR LOCATION: Periplasmic (By similarity)(Swiss-Prot: P66827).
SIMILARITY: Belongs to the Cu-Zn superoxide dismutase family(Swiss-Prot: P66827).
IMMUNOGENICITY: Induces antigen-specific Th1 immune response, as indicated by the specific induction of serum IgG2a, but not IgG1, antibodies and by the secretion of IFN-γ, but not IL-4, by the Cu/Zn SOD-stimulated splenocytes. Has been used for vaccine development [Ref6552:Vemulapalli et al., 2000][Ref6552:Vemulapalli et al., 2000][Ref6552:Vemulapalli et al., 2000].
MUTATION: An isogenic sodC mutant constructed from B abortus 2308 by gene replacement exhibited much greater susceptibility to killing by exogenous O(2)(-) than the parental 2308 strain, supporting a role for SodC in protecting this bacterium from O(2)(-) stress. The B abortus sodC mutant was much more sensitive to killing by cultured resident peritoneal macrophages from C57BL6J mice than 2308, and its attenuation in cultured murine macrophages was enhanced when these phagocytes were treated with gamma interferon. The attenuation of the B abortus sodC mutant in both resting and IFN-gamma -activated macrophages was alleviated in the presence of the NADPH oxidase inhibitor apocynin. Consistently, the B abortus sodC mutant also displayed significant attenuation in infected C57BL6J mice compared to the parental strain. These findings suggest that SodC protects B abortus 2308 from the respiratory burst of host macrophages [Ref6552:Vemulapalli et al., 2000]. |
10816475
|
|
|
virB8 from Brucella melitensis biovar Abortus 2308 |
Brucella melitensis biovar Abortus 2308 |
3827898
|
|
83269015
|
BAB2_0061 |
|
YP_418306.1 |
VirB8 |
Virulence factor |
MUTATION: virB8 mutant was attenuated by a mini-Tn5 transposon mutagenesis [Ref6484:Foulongne et al., 2000]. Attenuated non-polar virB2, virB4, virB8, virB9 and virB10 Brucella mutants are capable of penetrating cells as the same rate as the virulent wild-type Brucella, transit through EEA1-positive early compartments and then localize in LAMP1-positive compartments at early times of infection [Ref6466:Gorvel and Moreno, 2002]. |
10678941
12414149
|
|
|
xseA from Brucella melitensis biovar Abortus 2308 |
Brucella melitensis biovar Abortus 2308 |
3827916
|
|
83269378
|
BAB2_0475 |
|
YP_418669.1 |
exodeoxyribonuclease VII large subunit |
Virulence factor |
FUNCTION: Bidirectionally degrades single-stranded DNA into large acid-insoluble oligonucleotides, which are then degraded further into small acid-soluble oligonucleotides (By similarity)(Swiss-Prot: Q8FVR1).
CATALYTIC ACTIVITY: Exonucleolytic cleavage in either 5'- to 3'- or 3'- to 5'-direction to yield nucleoside 5'-phosphates(Swiss-Prot: Q8FVR1).
SUBUNIT: Heterooligomer composed of large and small subunits (By similarity)(Swiss-Prot: Q8FVR1).
SUBCELLULAR LOCATION: Cytoplasm (By similarity)(Swiss-Prot: Q8FVR1).
SIMILARITY: Belongs to the xseA family(Swiss-Prot: Q8FVR1).
MUTATION: xseA codes for an exodeoxyribonuclease. B. melitensis xseA mutant via signature-tagged mutagenesis is attenuated in vivo in mice [Ref6480:Lestrate et al., 2003]. |
14638795
|
|
|
narG from Brucella melitensis biovar Abortus 2308 |
Brucella melitensis biovar Abortus 2308 |
3827924
|
|
83269759
|
BAB2_0904 |
|
YP_419050.1 |
Nitrate reductase, alpha subunit:Prokaryotic molybdopterin oxidoreductase:Molybdopterin oxidoreductase:Molydopterin dinucleot... |
Virulence factor |
MUTATION: The narG gene encodes for an essential component of the dissimilatory nitrate reductase complex. This complex is encoded by the narGHIJ locus, which is present in the B suis genome together with the gene of the nitrite extrusion protein, narK. The narG mutant was unable to produce nitrite from nitrate [Ref412:Kohler et al., 2002]. A study with miniTn5 mutants of B. suis constitutively expressing gfp indicates that B. suis xx gene is required for intracellular multiplication in human macrophage THP-1 cells [Ref412:Kohler et al., 2002]. |
12438693
|
|
|
virB5 from Brucella melitensis biovar Abortus 2308 |
Brucella melitensis biovar Abortus 2308 |
3827978
|
|
83269018
|
BAB2_0064 |
|
YP_418309.1 |
attachment mediating protein virB5 homolog KO: K03200 type IV secretion system protein VirB5 |
Virulence factor |
MUTATION: A comparison of the VirB8 and VirB5 contents after induction of the B suis wild type and of virB5 and virB12 mutants further confirmed that the virB5 and virB12 genes belong to the same operon [Ref6543:Rouot et al., 2003].
Smooth strains of Brucella unable to replicate (ie, killed B suis or the avirulent mutant B suis virB5) exhibit delayed phagosome-lysosome fusion [Ref6544:Porte et al., 2003].
Polar mutations in the operon upstream of virB5 exert a greater effect on the expression of virB5 than they do on the expression of the downstream gene virB12. It indicates that in B abortus , regulatory elements other than the virB promoter may influence VirB12 protein levels [Ref6470:Sun et al., 2005].
Four independent mutants in virB5, virB9 or virB10 were highly attenuated in an in vitro infection model with human macrophages [Ref6467:O'Callaghan et al., 1999]. |
12595417
12595466
16113325
10510235
|
|
|
virB3 from Brucella melitensis biovar Abortus 2308 |
Brucella melitensis biovar Abortus 2308 |
3827980
|
|
83269020
|
BAB2_0066 |
|
YP_418311.1 |
Type IV secretory pathway, VirB3-like |
Virulence factor |
MUTATION: The B abortus virB3 gene is found to be essential for intracellular growth inside HeLa cells [Ref6469:Kim et al., 2003]. |
12761078
|
|
|
virB2 from Brucella melitensis biovar Abortus 2308 |
Brucella melitensis biovar Abortus 2308 |
3827981
|
|
83269021
|
BAB2_0067 |
|
YP_418312.1 |
type IV secretion system protein VirB2 KO: K03197 type IV secretion system protein VirB2 |
Virulence factor |
MUTATION: The Brucella abortus virB operon, encoding a type IV secretion system (T4SS), is required for intracellular replication and persistent infection in the mouse model. The products of the first two genes of the virB operon, virB1 and virB2, are predicted to be localized at the bacterial surface. Both mutants were shown to be nonpolar, as demonstrated by their ability to express the downstream gene virB5 during stationary phase of growth in vitro. Both VirB1 and VirB2 were essential for intracellular replication in J774 macrophages. The nonpolar virB2 mutant was unable to cause persistent infection in the mouse model, demonstrating the essential role of VirB2 in the function of the T4SS apparatus during infection [Ref6539:den et al., 2004].
Polar mutations in the virB1 to virB2 intergenic region or in virB2 reduced the detection of VirB5 to a greater extent than they did that of VirB12. A virB1 mutation also eliminates the transcription of virB12 in B suis [Ref6470:Sun et al., 2005]. |
15322008
16113325
|
|
|
omp10 from Brucella melitensis biovar Abortus 2308 |
Brucella melitensis biovar Abortus 2308 |
3828036
|
|
83269030
|
BAB2_0076 |
|
YP_418321.1 |
lipoprotein Omp10 |
Virulence factor |
SUBCELLULAR LOCATION: Outer membrane; lipid-anchor(Swiss-Prot: P0A3N9).
MISCELLANEOUS: Elicits an immune response in B.melitensis-infected sheep but not in B.abortus-infected cattle(Swiss-Prot: P0A3N9).
SIMILARITY: Belongs to the rhizobiaceae omp10 lipoprotein family(Swiss-Prot: P0A3N9).
MUTATION: Omp10 is an immunoreactive outer membrane lipoprotein. The omp10 mutant was dramatically attenuated for survival in mice and was defective for growth in minimal medium but was not impaired in intracellular growth in vitro, nor does it display clear modification of the outer membrane properties [Ref6473:Tibor et al., 2002]. |
12228280
|
|
|
cydB from Brucella melitensis biovar Abortus 2308 |
Brucella melitensis biovar Abortus 2308 |
3828142
|
|
83269608
|
BAB2_0727 |
|
YP_418899.1 |
Beta and gamma crystallin:Cytochrome bd ubiquinol oxidase, subunit II |
Virulence factor |
MUTATION: cydB is a gene that is part of the cydAB operon encoding cytochrome bd oxidase , which catalyzes an alternate terminal electron transport step in bacterial respiration. Transposon (Tn5) mutagenesis of B abortus cydB was severely attenuated for intracellular survival. Unlike the virulent strain 2308, the Brucella cydB::Tn5 mutant was severely compromised for survival in the spleens of inoculated mice [Ref6477:Endley et al., 2001]. The cydB and cydD mutants are also defective for the intracellular growth of B abortus and B suis, suggesting that functional cytochrome bd oxidase is required for growth in an intracellular environment [Ref6477:Endley et al., 2001]. |
11274104
|
|
|
divK from Brucella melitensis biovar Abortus 2308 |
Brucella melitensis biovar Abortus 2308 |
3828149
|
|
83269512
|
BAB2_0628 |
|
YP_418803.1 |
Response regulator receiver |
Virulence factor |
FUNCTIONAL GROUP: Regulation [Ref6462:Delrue et al., 2004].
FUNCTION: Response regulator [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Mice [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
flgI from Brucella melitensis biovar Abortus 2308 |
Brucella melitensis biovar Abortus 2308 |
3828215
|
|
0
|
BAB2_0153 |
|
- |
pseudo |
Virulence factor |
FUNCTIONAL GROUP: "Classical virulence factors", Secretion of transport system, Flagella [Ref6462:Delrue et al., 2004].
FUNCTION: P-ring [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Mice, but not in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
flgI from Brucella melitensis biovar Abortus 2308 |
Brucella melitensis biovar Abortus 2308 |
3828216
|
|
0
|
BAB2_0154 |
|
- |
pseudo |
Virulence factor |
FUNCTIONAL GROUP: "Classical virulence factors", Secretion of transport system, Flagella [Ref6462:Delrue et al., 2004].
FUNCTION: P-ring [Ref6462:Delrue et al., 2004].
MUTATION: Attenuated in Mice, but not in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
fliF from Brucella melitensis biovar Abortus 2308 |
Brucella melitensis biovar Abortus 2308 |
3828220
|
|
83269941
|
BAB2_1105 |
|
YP_419232.1 |
flagellar MS-ring protein |
Virulence factor |
FUNCTION: The M ring may be actively involved in energy transduction (By similarity)(Swiss-Prot: Q8FUS3).
SUBUNIT: The basal body constitutes a major portion of the flagellar organelle and consists of five rings (E,L,P,S, and M) mounted on a central rod. The M ring is integral to the inner membrane of the cell and may be connected to the flagellar rod via the S ring. The S (supramembrane ring) lies just distal to the M ring. The L and P rings lie in the outer membrane and the periplasmic space, respectively (By similarity)(Swiss-Prot: Q8FUS3).
SUBCELLULAR LOCATION: Inner membrane; multi-pass membrane protein (By similarity)(Swiss-Prot: Q8FUS3).
SIMILARITY: Belongs to the fliF family(Swiss-Prot: Q8FUS3).
MUTATION: fliF is a gene potentially coding for the MS ring, a basal component of the flagellar system. Its mutant through signature- tagged mutagenesis is attenuated in vivo. It implicate a role for flagella in virulenc [Ref6480:Lestrate et al., 2003]. |
14638795
|
|
|
gcvP from Brucella melitensis biovar Abortus 2308 |
Brucella melitensis biovar Abortus 2308 |
3828233
|
|
83269414
|
BAB2_0515 |
|
YP_418705.1 |
glycine dehydrogenase |
Virulence factor |
FUNCTION: The glycine cleavage system catalyzes the degradation of glycine. The P protein binds the alpha-amino group of glycine through its pyridoxal phosphate cofactor; CO(2) is released and the remaining methylamine moiety is then transferred to the lipoamide cofactor of the H protein (By similarity)(Swiss-Prot: Q8FVU9).
CATALYTIC ACTIVITY: Glycine + H-protein-lipoyllysine = H-protein-S-aminomethyldihydrolipoyllysine + CO(2)(Swiss-Prot: Q8FVU9).
COFACTOR: Pyridoxal phosphate (By similarity)(Swiss-Prot: Q8FVU9).
SUBUNIT: The glycine cleavage system is composed of four proteins: P, T, L and H (By similarity)(Swiss-Prot: Q8FVU9).
SIMILARITY: Belongs to the gcvP family(Swiss-Prot: Q8FVU9).
MUTATION: gcvP encodes for glycine dehydrogenase and is required for persistent infection in mouse model [Ref6482:Ficht, 2003]. |
12523983
|
|
|
gcvT from Brucella melitensis biovar Abortus 2308 |
Brucella melitensis biovar Abortus 2308 |
3828234
|
|
83269412
|
BAB2_0513 |
|
YP_418703.1 |
Glycine cleavage T protein (aminomethyl transferase) |
Virulence factor |
MUTATION: A study with miniTn5 mutants of B. suis constitutively expressing gfp indicates that B. suis gcvT gene is required for intracellular multiplication in human macrophage THP-1 cells [Ref412:Kohler et al., 2002]. |
12438693
|
|
|
glpK from Brucella melitensis biovar Abortus 2308 |
Brucella melitensis biovar Abortus 2308 |
3828238
|
|
0
|
BAB2_0796 |
|
- |
pseudo |
Virulence factor |
FUNCTION: Key enzyme in the regulation of glycerol uptake and metabolism(Swiss-Prot: Q8FWK8).
CATALYTIC ACTIVITY: ATP + glycerol = ADP + sn-glycerol 3-phosphate(Swiss-Prot: Q8FWK8).
PATHWAY: Glycerol utilization; first (rate-limiting) step(Swiss-Prot: Q8FWK8).
SIMILARITY: Belongs to the FGGY kinase family(Swiss-Prot: Q8FWK8).
MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. |
14979322
|
|
|
gltD from Brucella melitensis biovar Abortus 2308 |
Brucella melitensis biovar Abortus 2308 |
3828240
|
|
83269008
|
BAB2_0054 |
|
YP_418299.1 |
glutamate synthase subunit beta |
Virulence factor |
MUTATION: gltD encodes the small subunit of glutamate synthase. It is required for B. abortus growth as shown in signature-tagged transposon mutagenesis. It suggests that glutamate may serve as carbon and/or nitrogen sources during growth of B abortus [Ref6463:Hong et al., 2000]. |
10858227
|
|
|
gnd from Brucella melitensis biovar Abortus 2308 |
Brucella melitensis biovar Abortus 2308 |
3828241
|
|
83269060
|
BAB2_0109 |
|
YP_418351.1 |
6-phosphogluconate dehydrogenase |
Virulence factor |
MUTATION: gnd is involved in pentose phosphate pathway. It is essential for intracellular growth inside HeLa cells as shown by its Brucella suis miniTn5Km2 transposon mutation analysis. The mutant is attenuated in the mouse model [Ref6469:Kim et al., 2003]. |
12761078
|
|
|
hemH from Brucella melitensis biovar Abortus 2308 |
Brucella melitensis biovar Abortus 2308 |
3828247
|
|
83269029
|
BAB2_0075 |
|
YP_418320.1 |
ferrochelatase |
Virulence factor |
FUNCTION: Catalyzes the ferrous insertion into protoporphyrin IX(Swiss-Prot: P0A3D7).
CATALYTIC ACTIVITY: Protoporphyrin + Fe(2+) = protoheme + 2 H(+)(Swiss-Prot: P0A3D7).
PATHWAY: Protoheme biosynthesis; last step(Swiss-Prot: P0A3D7).
SUBCELLULAR LOCATION: Cytoplasm (By similarity)(Swiss-Prot: P0A3D7).
SIMILARITY: Belongs to the ferrochelatase family(Swiss-Prot: P0A3D7).
MUTATION: A hemH knockout B. abortus mutant displayed auxotrophy for hemin, defective intracellular survival inside J774 and HeLa cells, and lack of virulence in BALBc mice. This phenotype was overcome by complementing the mutant strain with a plasmid harboring wild-type hemH. These data demonstrate that B abortus synthesizes its own heme and also has the ability to use an external source of heme [Ref6472:Almirón et al., 2001]. |
11553564
|
|
|
LPS |
Brucella |
|
|
|
|
|
|
|
Virulence factor |
MUTATION: a wboA mutant led to the abolition of the O-side-chain synthesis resulting in rough LPS phenotype which was attenuated in mice. Restoration of wboA gene restored O-side-chain synthesis [Ref7281:McQuiston et al., 1999]. |
10417145
|
|
|
BMEI0066 |
Brucella melitensis bv. 1 str. 16M |
1195778
|
|
17986350
|
BMEI0066 |
NZ_GG703778 |
NP_538984 |
two component response regulator |
Virulence factor |
MUTATION: BMEI0066 deletion mutant fails to replicated in murine macrophages and is rapidly cleared from the spleens of experimentally infected BALB/c mice [Ref7314:Zhang et al., 2009]. |
19742243
|
|
|
asp24 from Brucella abortus |
Brucella abortus S2308 |
|
2352999
|
2353000
|
|
|
AAB69346.1 |
tRNA-Lys |
Virulence factor |
MUTATION: A asp24 mutation in Brucella abortus is attenuated in mice [Ref7373:Kahl-McDonagh et al., 2007]. |
17664263
|
|
|
bp26 from Brucella melitensis |
Brucella melitensis 16M |
|
|
1184104
|
|
|
|
BP26 |
Virulence factor |
MUTATION: A bp26 mutant in Brucella melitensis was attenuated in mice [Ref7374:Cloeckaert et al., 2004]. |
15246618
|
|
|
manA |
Brucella melitensis biovar Abortus 2308 |
3788792
|
|
|
BAB1_0562 |
|
|
|
Virulence factor |
MUTATION: a manAB double mutant is attenuated in mice [Ref7375:Kahl-McDonagh and Ficht, 2006]. |
16790778
|
|
|
pgk |
Brucella melitensis biovar Abortus 2308 |
3788256
|
|
82700518
|
BAB1_1742 |
AM040264 |
YP_415092 |
phosphoglycerate kinase |
Virulence factor |
MUTATION: A pgk mutant is attenuated in mice [Ref7376:Trant et al., 2010]. |
20194591
|
|
|
purK |
|
|
|
|
|
|
|
|
|
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