The Chlamydia trachomatis Inclusion Membrane Protein CpoS Counteracts STING-Mediated Cellular Surveillance and Suicide Programs.

Abstract

Evading cell death is critical for Chlamydia to maintain a replicative niche, but the underlying mechanisms are unknown. We screened a library of Chlamydia mutants for modulators of cell death. Inactivation of the inclusion membrane protein CpoS (Chlamydia promoter of survival) induced rapid apoptotic and necrotic death in infected cells. The protection afforded by CpoS is limited to the inclusion in which it resides, indicating that it counteracts a spatially restricted pro-death signal. CpoS-deficient Chlamydia induced an exacerbated type I interferon response that required the host cGAS/STING/TBK1/IRF3 signaling pathway. Disruption of STING, but not cGAS or IRF3, attenuated cell death, suggesting that STING mediates Chlamydia-induced cell death independent of its role in regulating interferon responses. CpoS-deficient strains are attenuated in their ability to propagate in cell culture and are cleared faster from the murine genital tract, highlighting the importance of CpoS for Chlamydia pathogenesis.

• Authors: Barbara S Sixt, Robert J Bastidas, Ryan Finethy, Ryan M Baxter, Victoria K Carpenter, Guido Kroemer, Jörn Coers, Raphael H Valdivia
• Journal: Cell host & microbe (Cell Host Microbe) Vol. 21 Issue 1 Pg. 113-121 (Jan 11 2017) ISSN: 1934-6069 [Electronic] United States
• PMID: 28041929 (Publication Type: Journal Article)
• Copyright: Copyright © 2017 Elsevier Inc. All rights reserved.

Chemical References

• Bacterial Proteins
• CpoS protein, Chlamydia trachomatis
• IRF3 protein, human
• Interferon Regulatory Factor-3
• Interferon Type I
• Membrane Proteins
• STING1 protein, human
• Protein Serine-Threonine Kinases
• TBK1 protein, human

Topics

• Animals
• Bacterial Proteins (genetics, metabolism)
• Cell Death (immunology)
• Chlamydia trachomatis (genetics, immunology, pathogenicity)
• Chlorocebus aethiops
• Female
• HeLa Cells
• Humans
• Interferon Regulatory Factor-3 (metabolism)
• Interferon Type I (immunology)
• Membrane Proteins (genetics, metabolism)
• Mice
• Mice, Inbred C57BL
• Protein Serine-Threonine Kinases (metabolism)
• Vero Cells