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. IMPORTANCE Chlamydia 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.
Faris et al. (Fri,) studied this question.