Infection-Dependent Modulation of the Host Adaptor Gab2 During Chlamydia trachomatis Intracellular Development

Chlamydia trachomatis (Ct) is an obligate intracellular bacterium that can cause severe reproductive complications, including infertility and pelvic inflammatory disease. Its pathogenicity depends on intracellular maturation, which involves differentiation between infectious elementary (EB) and replicative reticulate bodies within inclusion vacuoles. Ct is known to modulate host PI3K-AKT signaling during this process; however, the molecular basis of this regulation remains unclear. To elucidate this mechanism, we screened host factors linked to the PI3K-AKT axis using a PI3K-AKT-mTOR compound library comprising 319 inhibitors, and identified the adaptor protein Gab2 (GRB2-associated binding protein 2) as a new target molecule of Ct. Gab2 protein levels decreased during the late phase of infection, and Gab2 silencing impaired intracellular replication without affecting EB formation. These findings demonstrate that Ct infection modulates the host adaptor Gab2 during intracellular development and provide new insights into host-pathogen interactions underlying chlamydial maturation.