Abstract
Bacterial infection of mucosal epithelial cells triggers cell exfoliation to limit the dissemination of infection within the tissue. Therefore, mucosal pathogens must possess strategies to counteract cell extrusion in response to infection. This is critical to Chlamydia trachomatis because this pathogen spends most of its intracellular development in the non-infectious form. Thus, premature host cell extrusion is detrimental to the pathogen. The aim of this work is to demonstrate that C. trachomatis enhances host cell adhesion and possible mechanism involved in this enhanced cell adhesion. Live-cell total internal reflection fluorescence (TIRF) microscopy showed that focal adhesions in C. trachomatis infected cells displayed an increased stability. In contrast to the focal adhesions in mock-infected cells, which readily disassembled upon inhibition of myosin II by blebbisttin, those in infected cells remained intact. Super-resolution microscopy revealed a reorganization of focal adhesion-associated with paxillin and FAK in infected cells. Ectopic expression of type III effector TarP was found to localize to focal adhesions and mimicked the modulation and stabilization of focal adhesions, similar to C. trachomatis infection, in a vinculin-dependent manner. Lastly, the vinculin interacting domains of TarP that conferred stability in the presence of blebbistatin were shown also to be involved in the vertical reorganization of paxillin and the focal adhesion kinase, highlighting the direct modulation of focal adhesion stability by C. trachomatis.