Chlamydia trachomatis is an obligate intracellular pathogen causing the most common sexually transmitted bacterial infection in humans. During infection, the bacteria invade polarized columnar epithelial cells in the cervical transition zones and the upper female reproductive tract. To promote host invasion, C. trachomatis disrupts cell–cell junctions of polarized epithelia, but the underlying mechanisms are not well understood. In this new study, Dolat et al. report that the effector protein translocated early phosphoprotein (TepP), which is the most abundant effector protein in the infectious elementary body form of C. trachomatis, modulates epithelial tight junctions and promotes epithelial cell dispersion. The authors found that TepP associates with and promotes the phosphorylation of the host actin-binding protein EPS8 in Chlamydia-infected cells. Moreover, the authors were able to show that TepP modifies epithelial cell shape and disassembles cell–cell junctions in a manner dependent on EPS8. Epithelial cell dispersion during a primary infection enhanced the number of secondary inclusions, which suggests that TepP-mediated disruption of cell junctions and cell polarity increases the binding and entry of additional bacteria. In sum, the findings reveal how C. trachomatis repurposes a host cell factor to promote infection.