Cell membrane Complex Enzyme Eukaryotic cell or cell component Microbe-host cell complex Microorganism or its component Other Other -- ion Pathway or action Protein Protein or gene Protein or gene complex Protein or protein complex Bacterial membrane or virus envelope Cell membrane Cytoplasm Eukaryotic cell or cell component Extracellular Golgi Golgi membrane Intercellular Intracellular Mitochondria Nucleocapsid/Cytoplasm Organelle Organelle -- Cell membrane Organelle -- Endoplasmic reticulum Organelle -- ER Organelle -- Golgi Organelle -- Golgi membrane Organelle -- Nucleus Organelle -- Phagolysosome Organelle -- Phagosome Organelle -- Ribosome Other Phagolysosome Phagosome Chaperone Defense, immunity protein Enzyme Enzyme activator Enzyme inhibitor Genomic S segment Infection Ligand binding or carrier Motor Nucleic acid binding Other Signal transducer Toxicity Transcription factor binding Transcription regulation Transporter Unknown IC Inferred by Curator IDA Inferred from Direct Assay IEA Inferred from Electronic Annotation IEP Inferred from Expression Pattern IGI Inferred from Genetic Interaction IMP Inferred from Mutant Phenotype IPI Inferred from Physical Interaction ISS Inferred from Sequence or Structural Similarity NAS Non-traceable Author Statement ND No biological Data available RCA inferred from Reviewed Computational Analysis TAS Traceable Author Statement NR Not Recorded Lever MS, Nelson M, Ireland PI, Stagg AJ, Beedham RJ, Hall GA, Knight G, Titball RW Journal of medical microbiology Experimental aerogenic Burkholderia mallei (glanders) infection in the BALB/c mouse 2003 14614070 PubMed Lehavi O, Aizenstien O, Katz LH, Hourvitz A Harefuah [Glanders--a potential disease for biological warfare in humans and animals] 2002 12170562 PubMed Popov SF, Tikhonov NG, Piven' NN, Kurilov VIa, Dement'ev IP Zhurnal mikrobiologii, epidemiologii, i immunobiologii [The role of capsule formation in Burkholderia mallei for its persistence in vivo] 2000 10925882 PubMed Lopez J, Copps J, Wilhelmsen C, Moore R, Kubay J, St-Jacques M, Halayko S, Kranendonk C, Toback S, DeShazer D, Fritz DL, Tom M, Woods DE Microbes and infection / Institut Pasteur Characterization of experimental equine glanders 2003 14554254 PubMed Ulrich RL, DeShazer D Infection and immunity Type III secretion: a virulence factor delivery system essential for the pathogenicity of Burkholderia mallei 2004 14742564 PubMed Rainbow L, Hart CA, Winstanley C Journal of medical microbiology Distribution of type III secretion gene clusters in Burkholderia pseudomallei, B. thailandensis and B. mallei 2002 11990489 PubMed Anuntagool N, Sirisinha S Microbiology and immunology Antigenic relatedness between Burkholderia pseudomallei and Burkholderia mallei 2002 12008922 PubMed Fritz DL, Vogel P, Brown DR, Deshazer D, Waag DM Veterinary pathology Mouse model of sublethal and lethal intraperitoneal glanders (Burkholderia mallei) 2000 11105952 PubMed DeShazer D, Waag DM, Fritz DL, Woods DE Microbial pathogenesis Identification of a Burkholderia mallei polysaccharide gene cluster by subtractive hybridization and demonstration that the encoded capsule is an essential virulence determinant 2001 11373120 PubMed Burtnick MN, Brett PJ, Woods DE Journal of bacteriology Molecular and physical characterization of Burkholderia mallei O antigens 2002 11790757 PubMed Burkholderia mallei bacterium Function: Infection. Burkholderia mallei is a gram-negative, nonmotile, oxidase-positive bacterium responsible for a disease known as glanders in equines (horses, mules and donkeys) and occasionally in humans. The factors involved in the pathogenesis of Burkholderia mallei (B. mallei) infection remain relatively poorly defined at the molecular level. As a result, very little is known about the basic mechanism of B. mallei pathogenesis.(Burtnick et al., 2002)(DeShazer et al., 2001)(Anuntagool et al., 2002) Extracellular polysaccharide capsule Function: . Little is known about the virulence factors of B. mallei. The only virulence factor definitively shown to be essential for the pathogenicity of this bacterium is an extracellular polysaccharide capsule. The structure of B. mallei O-polysaccharide (probably component of LPS) is described as 3)-beta-D-glucopyranose-(1,3)-6-deoxy-alfa-L-talopyranose-(1-, in which the talose residue contains 2-O-methyl or 2-O-acetyl substituents.It should be noted that the R-type strains of B. mallei may be isolated as frequently as the S-type strains(Burtnick et al., 2002)(DeShazer et al., 2001)(Anuntagool et al., 2002)(Fritz et al., 2000) Type III Secretion System Function: Transporter. Type III secretion systems (TTSS) are implicated in the pathogenicity of several gram-negative bacterial pathogens. The B. mallei TTSS encodes 30 open reading frames (ORFs) and shares genetic similarity to some gram-negative bacteria. Mutagenesis analysis demonstrated that a functional TTSS was required for the full pathogenicity of B. mallei in the experimental animal models. It is not clear yet what secreted effector molecules (virulence factors) are involved in translocation process from B. mallei bacteria to the host cells. Further studies will be needed to identify putative effectors and decipher the complex molecular mechanisms associated with this TTSS.(Rainbow et al., 2002)(Ulrich et al., 2004) The virulence factors Function: . The virulence factors and pathogenesis of the disease caused by B. mallei are distinctive, still elusive, and remain to be investigated. The losing of the capsule appears to decrease in virulence, suggesting that capsule is an important virulence factor for B. mallei, as it is for other pathogenic bacteria. B. mallei can survive in the presence of 30% normal human serum (NHS) over the course of 18 h while the strains lacking O-polysaccharide are completely killed following 2-h incubation in 30% NHS. These results suggest that B. mallet O-polysaccharide plays a crucial role in the serum resistance of this organism. The TTSS plays an essential role in the virulence of B. mallei and is required for intracellular replication within murine macrophage-like cells.(Burtnick et al., 2002)(Fritz et al., 2000)(Ulrich et al., 2004)(Lopez et al., 2003) B. mallei cell spread and persistence Function: . There is little information about pathologic findings in humans infected with B. mallei. The bacteria tend to localize at the site of entry (skin, nasal or laryngeal mucosa) and induce formation of nodules that ultimately ulcerate, resulting in lymphangitis and lymphadenopathy. When the B. mallei bacteria are spread systemically, many tissues can be seeded. These tissues include skin, skeletal muscle, bone, joints, less commonly brain, and rarely nasal or ocular. The lungs, liver, and spleen are often affected. In the subacute course of infection, the encapsulated forms of B. mallei parasitized mainly in the cells of the system of mononuclear phagocytes in the liver, the spleen and the lungs. The capsule formed by B. mallei is the factor facilitating its persistence in the host.(Fritz et al., 2000)(Popov et al., 2000) Host cell necrosis Function: . Infection of the lungs by B. mallei is resulted in foci of acute inflammation and necrosis. Necrosis of the tracheobronchial tree and pustular skin lesions characterize acute infection with B. mallei.(Lopez et al., 2003)(Lehavi et al., 2002)(Lever et al., 2003)