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

Publication date: Available online 29 December 2016
Source:Cell Host & Microbe
Author(s): Barbara S. Sixt, Robert J. Bastidas, Ryan Finethy, Ryan M. Baxter, Victoria K. Carpenter, Guido Kroemer, Jörn Coers, Raphael H. Valdivia
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.

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Teaser

Evading cell death is critical for Chlamydia trachomatis to maintain a replicative niche. Sixt et al. show that the Chlamydia effector protein CpoS counteracts STING-mediated pro-death signals and type I IFN responses in response to Chlamydia-containing vacuoles, which enables optimal intracellular bacterial growth and survival in the murine genital tract.


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