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PMID:23813730
| Citation |
Weber, MM, Chen, C, Rowin, K, Mertens, K, Galvan, G, Zhi, H, Dealing, CM, Roman, VA, Banga, S, Tan, Y, Luo, ZQ and Samuel, JE (2013) Identification of Coxiella burnetii type IV secretion substrates required for intracellular replication and Coxiella-containing vacuole formation. J. Bacteriol. 195:3914-24 |
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| Abstract |
Coxiella burnetii, the etiological agent of acute and chronic Q fever in humans, is a naturally intracellular pathogen that directs the formation of an acidic Coxiella-containing vacuole (CCV) derived from the host lysosomal network. Central to its pathogenesis is a specialized type IVB secretion system (T4SS) that delivers effectors essential for intracellular replication and CCV formation. Using a bioinformatics-guided approach, 234 T4SS candidate substrates were identified. Expression of each candidate as a TEM-1 β-lactamase fusion protein led to the identification of 53 substrates that were translocated in a Dot/Icm-dependent manner. Ectopic expression in HeLa cells revealed that these substrates trafficked to distinct subcellular sites, including the endoplasmic reticulum, mitochondrion, and nucleus. Expression in Saccharomyces cerevisiae identified several substrates that were capable of interfering with yeast growth, suggesting that these substrates target crucial host processes. To determine if any of these T4SS substrates are necessary for intracellular replication, we isolated 20 clonal T4SS substrate mutants using the Himar1 transposon and transposase. Among these, 10 mutants exhibited defects in intracellular growth and CCV formation in HeLa and J774A.1 cells but displayed normal growth in bacteriological medium. Collectively, these results indicate that C. burnetii encodes a large repertoire of T4SS substrates that play integral roles in host cell subversion and CCV formation and suggest less redundancy in effector function than has been found in the comparative Legionella Dot/Icm model. |
| Links |
PubMed PMC3754607 Online version:10.1128/JB.00071-13 |
| Keywords |
Animals; Bacterial Proteins/genetics; Bacterial Proteins/metabolism; Cell Line; Computational Biology; Coxiella burnetii/genetics; Coxiella burnetii/growth & development; Coxiella burnetii/metabolism; DNA, Bacterial/genetics; Epithelial Cells/microbiology; Humans; Macrophages/microbiology; Mice; Mutagenesis, Insertional; Protein Transport; Saccharomyces cerevisiae/growth & development; Vacuoles/microbiology; Virulence Factors/genetics; Virulence Factors/metabolism |
Significance
Annotations
| Gene product | Qualifier | GO Term | Evidence Code | with/from | Aspect | Extension | Notes | Status |
|---|---|---|---|---|---|---|---|---|
| GO:0044165: host cell endoplasmic reticulum |
ECO:0000314: |
C |
Figure 2B. C. burnetii secretion substrates target distinct subcellular compartments when ectopically expressed in HeLa cells. Cbu0372 colocalizes with the endoplasmic reticulum marker calnexin (arrow indication) |
complete | ||||
| GO:0044165: host cell endoplasmic reticulum |
ECO:0000314: |
C |
Figure 2B. C. burnetii secretion substrates target distinct subcellular compartments when ectopically expressed in HeLa cells. Cbu1576 colocalization with the endoplasmic reticulum marker calnexin (arrow indication). |
complete | ||||
| GO:0033650: host cell mitochondrion |
ECO:0000314: |
C |
Figure 2B. C. burnetii secretion substrates target distinct subcellular compartments when ectopically expressed in HeLa cells. CbuA0020 colocalizes with the mitochondrial marker CoxIV (arrow indication). |
complete | ||||
| GO:0042025: host cell nucleus |
ECO:0000314: |
C |
Figure 2. C. burnetii secretion substrates target distinct subcellular compartments when ectopically expressed in HeLa cells. Colocalization of Cbu0388 with the host cell nucleus could be demonstrated. |
complete | ||||
Notes
See also
References
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