PHIDIAS: Pathogen-Host Interaction Data Integration and Analysis System

Phinet Name: Coxiella burnetii
Phinet Information
Pathogen Name: Coxiella burnetii
Pathogen NIAID Category: NIAID Category B
Bio-objects
Bio-object 1: Bacterial Ligand
Type: Protein or gene Location: Extracellular Function: Ligand binding or carrier Description: Internalization into host cells occurs by microfilament-dependent parasite-directed endocytosis. The bacterial ligand(s) and host receptor mediating this process are undefined (Heinzen et al., 1999). In vivo, the initial target is the alveolar macrophage, although the organism can subsequently disseminate to replicate within a wide variety of tissues (Heinzen et al., 1999). Infection by either small cell variants (SCVs) or large cell variants (LCVs) eventually results in parasitophorous vacuoles harboring a mixture of cell types (Heinzen et al., 1999).(<a href="#reference5275">Heinzen et al., 1999</a>)
Bio-object 2: C. burnetii in Cytoplasm
Type: Microbe-host cell complex Location: Cytoplasm Description: Occasionally, C. burnetii has been observed 'free' in the cytoplasm. The possibility that these free rickettsiae may have a closely opposed host membrane has not been excluded (Baca and Paretsky, 1983).(<a href="#reference5276">Baca et al., 1983</a>)
Bio-object 3: C. burnetii in Phagolysosome
Type: Microbe-host cell complex Location: Phagolysosome Description: Cytochemical investigation revealed that the rickettsiae-containing vacuoles are phagolysosomes (Baca and Paretsky, 1983). Once entry into the cell is achieved, both phases of C. burnetii proliferate within vacuoles which eventually fuse and form a single vacuole which occupies most of the cell's volume. The infected cell attains a size several diameters greater than uninfected cells. The nucleus and cytoplasm become displaced to the cell's periphery (Baca and Paretsky, 1983).The lysosomal markers 5'-nucleotidase, acid phosphatase, cathepsin D and lysosomal-associated membrane glycoproteins 1 and 2 co-localize with the lumen of the parasitophorous vacuole (PV) or PV membrane, and the PV acidifies to a pH of approximately 4.8. C. burnetii has an absolute requirement for this moderately acidic pH to activate metabolism and exploits the only intracellular niche capable of establishing such a pH. The organism replicates to high numbers within this vacuole, albeit at a slow replication rate (8-12 h doubling time), despite the presence of toxic host factors, such as acid hydrolases and defensins, which are normally considered bactericidal (Heinzen et al., 1999).(<a href="#reference5276">Baca et al., 1983</a>)(<a href="#reference5275">Heinzen et al., 1999</a>)
Bio-object 4: C. burnetii in Phagosome
Type: Microbe-host cell complex Location: Phagosome Description: The nascent parasite-containing phagosomes mature through the endocytic pathway, eventually acquiring the properties of secondary lysosomes (Baca and Paretsky, 1983).(<a href="#reference5276">Baca et al., 1983</a>)
Bio-object 5: Cell Receptor
Type: Protein or gene Location: Cell membrane Function: Ligand binding or carrier Description: Internalization into host cells occurs by microfilament-dependent parasite-directed endocytosis. The bacterial ligand(s) and host receptor mediating this process are undefined (Heinzen et al., 1999).Studies on the nature of the C. burnetii attachment site on the L-929 cell surface showed that only pronase and subtilisin treatment of the L cells significantly inhibited attachment of C. burnetii. This provided circumstantial evidence that proteins are at or near the site of Coxiella attachment. Whether or not there is a specific component to which the parasite attaches is as yet unknown (Baca and Paretsky, 1983).(<a href="#reference5275">Heinzen et al., 1999</a>)(<a href="#reference5276">Baca et al., 1983</a>)
Bio-object 6: Large Cell Variant (LCV) Extracellular
Type: Microorganism or its component Location: Extracellular Description: The observation that LCVs are infectious in vitro might have little relevance to natural transmission and infection because the fragile LCVs probably do not persist extracellularly in an infectious form for extended periods (Heinzen et al., 1999). The LCV are fragile, probably not surviving extracellularly for extended periods (Varghees et al., 2002).(<a href="#reference5275">Heinzen et al., 1999</a>)(<a href="#reference5278">Varghees et al., 2002</a>)
Bio-object 7: Large Cell Variant (LCV) in Phagolysosome
Type: Microbe-host cell complex Location: Phagolysosome Description: Several reports present electron microscopic evidence suggesting that C. burnetii exhibits two morphological forms, a large and small form (Baca and Paretsky, 1983). A typical C. burnetii parasitophorous vacuole contains a continuum of morphological forms, within which are the morphologically distance large cell variants (LCV) and small cell variants (SCV), which can be separated on the basis of different buoyant densities (Heinzen et al., 1999). The LCVs can reach a length exceeding 1.0 um and are similar in form to typical Gram-negative bacteria in that they posess a clearly distinguishable outer membrane, periplasmic space and cytoplasmic membrane. The LCVs are more pleiomorphic than the SCVs, with a thinner cell wall and a very dispersed nucleoid (Heinzen et al., 1999). Evidence suggests that the LCV are more metabolically and replicatively active than SCVs. As such, they might play a more important role than the SCV in cell-to-cell spread within the host (Heinzen et al., 1999). The LCV and the SCV divide by binary fission, and both are infectious in in vitro and in vivo models (Heinzen et al., 1999).(<a href="#reference5276">Baca et al., 1983</a>)(<a href="#reference5275">Heinzen et al., 1999</a>)
Bio-object 8: Small Cell Variant (SCV) Extracellular
Type: Microorganism or its component Location: Extracellular Description: The SDC and SCV may represent the forms of the bacteria likely to survive as infectious particles extracellularly (Varghees et al., 2002).(<a href="#reference5278">Varghees et al., 2002</a>)
Bio-object 9: Small Cell Variant (SCV) in Phagolysosome
Type: Microbe-host cell complex Location: Phagolysosome Description: Several reports present electron microscopic evidence suggesting that C. burnetii exhibits two morphological forms, a large and small form (Baca and Paretsky, 1983). A typical C. burnetii parasitophorous vacuole contains a continuum of morphological forms, within which are the morphologically distinct large cell variants (LCV) and small cell variants (SCV), which can be separated on the basis of different buoyant densities (Heinzen et al., 1999). The SCVs are typically between 0.2 and 0.5 um in size, rod shaped and very compact. The visible periplasmic space is replaced with an electron-dense region bounded by the outer and cytoplasmic membranes. The most distinctive ultrastructural characteristic of the SCV is the electron-dense chromatin. The SCVs also harbor a complex system of internal membranes arranged in whorls that could be contiguous with the cytoplasmic membrane (Heinzen et al., 1999). The LCV and the SCV divide by binary fission, and both are infectious in in vitro and in vivo models (Heinzen et al., 1999)>(<a href="#reference5276">Baca et al., 1983</a>)(<a href="#reference5275">Heinzen et al., 1999</a>)
Bio-object 10: Spore-like Particle (SLP) in Phagolysosome
Type: Microbe-host cell complex Location: Phagolysosome Description: The possible biogenesis of a spore-like particle (SLP) has also been suggested. SLPs have been observed as electron-dense polar bodies in the large cell variants (LCV) and are speculated to have endospore-like properties. McCaul and Williams surmise that the small cell variants (SCV) and/or SLPs are extracellular survival stages (Heinzen et al., 1999).The notion of sporogenesis by C. burnetii is of continuing debate. This alternative form of replication was originally proposed by McCaul and Williams in 1981 and is based on morphological data gathered by TEM examination of purified cells. The impetus for this proposal is the occasional appearance of an electron-dense, membrane bound SLP within the LCVs. SLPs are approximately 130-170 nm in diameter and are bounded by a limiting membrane. They are observed only in those cells morphologically identified as LCVs, with formation thought to occur by a process that resembles asymmetric cell division. From the center outward, the SLP is believed to be composed of a dense core containing DNA,a system of membranes, peptidoglycan and outer membrane. The antigenic character of the SLP remain elusive (Heinzen et al., 1999). A major impediment to the study of the SLP is an inability to obtain these particles in pure form. Until SLPS are purified and shown to be infectious, the existence of this developmental form in the C. burnetii developmental cycle must be considered hypothetical (Heinzen et al., 1999).(<a href="#reference5275">Heinzen et al., 1999</a>)
Interactions
Interaction 1: Interaction1
Input Objects: Bacterial Ligand, Cell Receptor Output Objects: C. burnetii in Phagosome GO Evidence Code: No biological Data available Description: Internalization into host cells occurs by microfilament-dependent parasite-directed endocytosis. The bacterial ligand(s) and host receptor mediating this process are undefined (Heinzen et al., 1999)(<a href="#reference5275">Heinzen et al., 1999</a>)
Interaction 2: Interaction2
Input Objects: C. burnetii in Phagosome Output Objects: C. burnetii in Phagolysosome GO Evidence Code: No biological Data available Description: The nascent parasite-containing phagosomes mature though the endocytic pathway, eventually acquiring the properties of secondary lysosomes (Heinzen et al., 1999).Maturation of nascent C. burnetii PV through the endocytic pathway is somewhat altered. For example, eventual fusion of PV harboring viable C. burnetii with the lysosomal compartment takes approximately 4-6 h as opposed to 1 h for vacuoles containing dead C. burnetii or latex beads. Moreover, a recent report indicates that C. burnetii PV intersect the cellular autophagy pathway and take on characteristics of autophagolysosomes. Mature C. burnetii PV also display unusual fusogenicity with other vacuoles within the endolysosomal pathway (Howe et al., 2003). Transit of nascent PV through the endocytic pathway to ultimately acquire lysosomal markers appears to occur irrespective of Coxiella protein synthesis (Howe et al., 2003).(<a href="#reference5275">Heinzen et al., 1999</a>)(<a href="#reference5277">Howe et al., 2003</a>)
Interaction 3: Interaction3
Input Objects: C. burnetii in Phagolysosome Output Objects: C. burnetii in Cytoplasm, Small Cell Variant (SCV) in Phagolysosome, Large Cell Variant (LCV) in Phagolysosome GO Evidence Code: No biological Data available Description: Several reports present electron microscopic evidence suggesting that C. burnetii exhibits two morphological forms, a large and small form (Baca and Paretsky, 1983). A typical C. burnetii parasitophorous vacuole contains a continuum of morphological forms, within which are the morphologically distinct large cell variants (LCV) and small cell variants (SCV), which can be separated on the basis of different buoyant densities (Heinzen et al., 1999).(<a href="#reference5275">Heinzen et al., 1999</a>)
Interaction 4: Interaction4
Input Objects: Small Cell Variant (SCV) in Phagolysosome Output Objects: Small Cell Variant (SCV) Extracellular GO Evidence Code: No biological Data available Description: The bacteria are released from the host cell as a result of host cell lysis or possibly exocytosis, and these 'naturally released' C. burnetii infect other host cells (Howe and Mallavia, 2000).(<a href="#reference5279">Howe et al., 2000</a>)
Interaction 5: Interaction6
Input Objects: Large Cell Variant (LCV) in Phagolysosome Output Objects: Spore-like Particle (SLP) in Phagolysosome, Large Cell Variant (LCV) Extracellular GO Evidence Code: No biological Data available Description: The bacteria are released from the host cell as a result of host cell lysis or possibly exocytosis, and these 'naturally released' C. burnetii infect other host cells (Howe and Mallavia, 2000).(<a href="#reference5279">Howe et al., 2000</a>)
Pathways

Phinet Name: Coxiella burnetii