CT135 mediates the resistance of Chlamydia trachomatis to primate interferon gamma stimulated immune defenses

Mark C Fernandez; Yvonne Cosgrove Sweeney; Robert J Suchland; Steven J Carrell; Olusegun O Soge; Isabelle Q Phan; Daniel D Rockey; Dorothy L Patton; Kevin Hybiske

doi:10.1016/j.isci.2024.110143

CT135 mediates the resistance of Chlamydia trachomatis to primate interferon gamma stimulated immune defenses

iScience. 2024 May 28;27(6):110143. doi: 10.1016/j.isci.2024.110143. eCollection 2024 Jun 21.

Authors

Mark C Fernandez^{1

2}, Yvonne Cosgrove Sweeney³, Robert J Suchland⁴, Steven J Carrell⁵, Olusegun O Soge^{1

4}, Isabelle Q Phan^{6

7}, Daniel D Rockey⁵, Dorothy L Patton³, Kevin Hybiske^{2

4}

Affiliations

¹ Department of Global Health, University of Washington, Seattle, WA 98109, USA.
² Center for Emerging and Re-emerging Infectious Diseases, University of Washington, Seattle, WA 98109, USA.
³ Department of Obstetrics and Gynecology, University of Washington, Seattle, WA 98109, USA.
⁴ Department of Medicine, University of Washington, Seattle, WA 98109, USA.
⁵ Department of Biomedical Sciences, Oregon State University, Corvallis, OR 97331, USA.
⁶ Seattle Structural Genomics Center for Infectious Disease, Seattle, WA 98109, USA.
⁷ Center for Global Infectious Disease Research, Seattle Children's Hospital, Seattle, WA 98109, USA.

Abstract

Evading host innate immune defenses is a critical feature of Chlamydia trachomatis infections, and the mechanisms used by C. trachomatis to subvert these pathways are incompletely understood. We screened a library of chimeric C. trachomatis mutants for genetic factors important for interference with cell-autonomous immune defenses. Mutant strains with predicted truncations of the inclusion membrane protein CT135 were susceptible to interferon gamma-activated immunity in human cells. CT135 functions to prevent host-driven recruitment of ubiquitin and p62/SQSTM to the inclusion membrane. In a nonhuman primate model of C. trachomatis infection, a CT135-deficient strain was rapidly cleared, highlighting the importance of this virulence factor for C. trachomatis pathogenesis. Analysis of CT135 phenotypes in primary macaque cells revealed that cell-autonomous immune defenses against C. trachomatis are conserved between humans and nonhuman primates and connects mechanistic findings with in vivo infection outcomes.

Keywords: Microbiology; Mycology; immunology.

Abstract

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