Chlamydia trachomatis Polymorphic Membrane Protein D Is a Virulence Factor Involved in Early Host-Cell Interactions
ABSTRACTChlamydia trachomatisis an obligate intracellular mucosotropic pathogen of significant medical importance. It is the etiological agent of blinding trachoma and bacterial sexually transmitted diseases, infections that afflict hundreds of millions of people globally. TheC. trachomatispolymorphic membrane protein D (PmpD) is a highly conserved autotransporter and the target of broadly cross-reactive neutralizing antibodies; however, its role in host-pathogen interactions is unknown. Here we employed a targeted reverse genetics approach to generate apmpDnull mutant that was used to define the role of PmpD in the pathogenesis of chlamydial infection. We show thatpmpDis not an essential chlamydial gene and thepmpDnull mutant has no detectable deficiency in cultured murine cells or in a murine mucosal infection model. Notably, however, thepmpDnull mutant was significantly attenuated for macaque eyes and cultured human cells. A reduction inpmpDnull infection of human endocervical cells was associated with a deficiency in chlamydial attachment to cells. Collectively, our results show that PmpD is a chlamydial virulence factor that functions in early host-cell interactions. This study is the first of its kind using reverse genetics to evaluate the contribution of aC. trachomatisgene to disease pathogenesis.