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

Publication ,  Journal Article
Sixt, BS; Bastidas, RJ; Finethy, R; Baxter, RM; Carpenter, VK; Kroemer, G; Coers, J; Valdivia, RH
Published in: Cell Host Microbe
January 11, 2017

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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Published In

Cell Host Microbe

DOI

EISSN

1934-6069

Publication Date

January 11, 2017

Volume

21

Issue

1

Start / End Page

113 / 121

Location

United States

Related Subject Headings

  • Vero Cells
  • Protein Serine-Threonine Kinases
  • Mice, Inbred C57BL
  • Mice
  • Membrane Proteins
  • Interferon Type I
  • Interferon Regulatory Factor-3
  • Immunology
  • Humans
  • Hela Cells
 

Citation

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Sixt, B. S., Bastidas, R. J., Finethy, R., Baxter, R. M., Carpenter, V. K., Kroemer, G., … Valdivia, R. H. (2017). The Chlamydia trachomatis Inclusion Membrane Protein CpoS Counteracts STING-Mediated Cellular Surveillance and Suicide Programs. Cell Host Microbe, 21(1), 113–121. https://doi.org/10.1016/j.chom.2016.12.002
Sixt, Barbara S., Robert J. Bastidas, Ryan Finethy, Ryan M. Baxter, Victoria K. Carpenter, Guido Kroemer, Jörn Coers, and Raphael H. Valdivia. “The Chlamydia trachomatis Inclusion Membrane Protein CpoS Counteracts STING-Mediated Cellular Surveillance and Suicide Programs.Cell Host Microbe 21, no. 1 (January 11, 2017): 113–21. https://doi.org/10.1016/j.chom.2016.12.002.
Sixt BS, Bastidas RJ, Finethy R, Baxter RM, Carpenter VK, Kroemer G, et al. The Chlamydia trachomatis Inclusion Membrane Protein CpoS Counteracts STING-Mediated Cellular Surveillance and Suicide Programs. Cell Host Microbe. 2017 Jan 11;21(1):113–21.
Sixt, Barbara S., et al. “The Chlamydia trachomatis Inclusion Membrane Protein CpoS Counteracts STING-Mediated Cellular Surveillance and Suicide Programs.Cell Host Microbe, vol. 21, no. 1, Jan. 2017, pp. 113–21. Pubmed, doi:10.1016/j.chom.2016.12.002.
Sixt BS, Bastidas RJ, Finethy R, Baxter RM, Carpenter VK, Kroemer G, Coers J, Valdivia RH. The Chlamydia trachomatis Inclusion Membrane Protein CpoS Counteracts STING-Mediated Cellular Surveillance and Suicide Programs. Cell Host Microbe. 2017 Jan 11;21(1):113–121.
Journal cover image

Published In

Cell Host Microbe

DOI

EISSN

1934-6069

Publication Date

January 11, 2017

Volume

21

Issue

1

Start / End Page

113 / 121

Location

United States

Related Subject Headings

  • Vero Cells
  • Protein Serine-Threonine Kinases
  • Mice, Inbred C57BL
  • Mice
  • Membrane Proteins
  • Interferon Type I
  • Interferon Regulatory Factor-3
  • Immunology
  • Humans
  • Hela Cells