Regulation of chlamydial infection by host autophagy and vacuolar ATPase-bearing organelles.

Abstract

As arguably the most successful parasite, Chlamydia is an obligate intracellular bacterium replicating inside a vacuole of eukaryotic host cells. The chlamydial vacuole does not fuse with the defense cell organelle lysosome. We previously showed that chlamydial infection increases markers of autophagy, an innate antimicrobial activity requiring lysosomal function. However, the work presented here demonstrates that p62, an autophagy protein that is degraded in lysosomes, either remained unchanged or increased in chlamydia-infected human epithelial, mouse fibroblast, and mouse macrophage cell lines. In addition, the activities of three lysosomal enzymes analyzed were diminished in chlamydia-infected macrophages. Bafilomycin A1 (BafA), a specific inhibitor of vacuolar ATPase (vATPase) required for lysosomal function, increased the growth of the human pathogen Chlamydia trachomatis (L2) in wild-type murine fibroblasts and macrophages but inhibited growth in the autophagy-deficient ATG5(-/-) fibroblasts. BafA exhibited only slight inhibition or no effect on L2 growth in multiple human genital epithelial cell lines. In contrast to L2, the mouse pathogen Chlamydia muridarum (MoPn) was consistently inhibited by BafA in all cell lines examined, regardless of species origin and autophagy status. Finally, L2 but not MoPn grew more efficiently in the ATG5(-/-) cells than in wild-type cells. These results suggest that there are two types of vATPase-bearing organelles that regulate chlamydial infection: one supports chlamydial infection, while the other plays a defensive role through autophagy when cells are artificially infected with certain chlamydiae that have not been adapted to the host species.

• Authors: Muhammad Yasir, Niseema D Pachikara, Xiaofeng Bao, Zui Pan, Huizhou Fan
• Journal: Infection and immunity (Infect Immun) Vol. 79 Issue 10 Pg. 4019-28 (Oct 2011) ISSN: 1098-5522 [Electronic] United States
• PMID: 21807906 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Enzyme Inhibitors
• Macrolides
• bafilomycin A1
• Vacuolar Proton-Translocating ATPases

Topics

• Animals
• Autophagy
• Cell Line
• Chlamydia Infections (metabolism, microbiology, pathology)
• Chlamydia muridarum (drug effects, growth & development, pathogenicity)
• Chlamydia trachomatis (drug effects, growth & development, pathogenicity)
• Enzyme Inhibitors (pharmacology)
• Epithelial Cells (microbiology)
• Fibroblasts (microbiology)
• HeLa Cells
• Humans
• Lysosomes (enzymology, metabolism)
• Macrolides (pharmacology)
• Macrophages (microbiology)
• Mice
• Organelles (enzymology)
• Vacuolar Proton-Translocating ATPases (antagonists & inhibitors, metabolism)