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
Affiliations
Mark C. Fernandez
Department of Global Health, University of Washington, Seattle, WA 98109, USA; Center for Emerging and Re-emerging Infectious Diseases, University of Washington, Seattle, WA 98109, USA
Yvonne Cosgrove Sweeney
Department of Obstetrics and Gynecology, University of Washington, Seattle, WA 98109, USA
Robert J. Suchland
Department of Medicine, University of Washington, Seattle, WA 98109, USA
Steven J. Carrell
Department of Biomedical Sciences, Oregon State University, Corvallis, OR 97331, USA
Olusegun O. Soge
Department of Global Health, University of Washington, Seattle, WA 98109, USA; Department of Medicine, University of Washington, Seattle, WA 98109, USA
Isabelle Q. Phan
Seattle Structural Genomics Center for Infectious Disease, Seattle, WA 98109, USA; Center for Global Infectious Disease Research, Seattle Children’s Hospital, Seattle, WA 98109, USA
Daniel D. Rockey
Department of Biomedical Sciences, Oregon State University, Corvallis, OR 97331, USA
Dorothy L. Patton
Department of Obstetrics and Gynecology, University of Washington, Seattle, WA 98109, USA
Kevin Hybiske
Center for Emerging and Re-emerging Infectious Diseases, University of Washington, Seattle, WA 98109, USA; Department of Medicine, University of Washington, Seattle, WA 98109, USA; Corresponding author
Summary: 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.
