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The Chlamydia trachomatis-secreted effector protein CT181 binds to Mcl-1 and prolongs neutrophil survival
Journal article   Open access   Peer reviewed

The Chlamydia trachomatis-secreted effector protein CT181 binds to Mcl-1 and prolongs neutrophil survival

Robert Faris, Rebecca Koch, Paige McCaslin, Naveen Challagundla, Brianna Steiert, Shelby E. Andersen, Alix McCullough, Parker Smith, C. A. Jabeena, Peter Yau, …
mBio, e0035726
05/15/2026
DOI: 10.1128/mbio.00357-26
PMCID: PMC13251465
PMID: 42138418
url
https://doi.org/10.1128/mbio.00357-26View
Published (Version of record) Open Access

Abstract

Chlamydia trachomatis (C.t.) infections can lead to severe complications due to the pathogen’s ability to evade the host immune response, often resulting in asymptomatic infections. The mechanisms underlying this immune subversion remain incompletely understood, but likely involve specific bacterial effector proteins. Here, we identify CT181 as a novel effector that binds to Mcl-1, a key regulator of neutrophil survival. While a C.t. CT181 mutant exhibited only modest defects in epithelial cell replication and inclusion development, it was required for C.t. survival in neutrophils, which correlated with elevated Mcl-1 levels in cells infected with wild-type C.t. Using a murine infection model, we demonstrate that CT181 contributes to C.t. colonization and inflammatory cytokine production in vivo. Our findings establish CT181 as the first bacterial effector protein known to bind Mcl-1 and show that it is associated with prolonged neutrophil survival, revealing a novel strategy by which C.t. promotes immune dysregulation, facilitating bacterial persistence while driving C.t. pathogenesis.IMPORTANCEChlamydia trachomatis is an obligate intracellular pathogen that must evade early immune defenses to establish infection. This study identifies CT181 as a previously undescribed secreted effector that associates with the host pro-survival protein Mcl-1 and is linked to prolonged neutrophil survival during infection. Neutrophils, which normally undergo rapid apoptosis, persist longer when infected with wild-type C. trachomatis, whereas loss of CT181 reduces bacterial survival in these cells. In a mouse model of infection, the CT181 mutant exhibits reduced bacterial burden and diminished inflammatory responses, including neutrophil recruitment and cytokine production. Together, these findings highlight CT181 as a bacterial factor that contributes to host cell survival and immune modulation during C. trachomatis infection, underscoring the complex strategies used by intracellular pathogens to persist within the host.
 Signal Transduction Chemokines Chlamydia Clinical Microbiology and Infectious Diseases Cytokine Signaling Editor’s Pick Effector Proteins Genitourinary Infections Host-Microbial Interactions Host-Pathogen Signal Modulation Innate Immunity Microbial Pathogenesis and Immunology Microbial Physiology and Genetics Phagocytic Cell Function Phagocytic Cells (Macrophages, Neutrophils) Polymorphonuclear Phagocytosis Protein Secretion Systems Research Article Role in Virulence and Host Interaction Virulence Factors

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