A renewed tool kit to explore Chlamydia pathogenesis: from molecular genetics to new infection models

Abstract

Chlamydia trachomatisis the most prevalent sexually transmitted bacterial pathogen and the leading cause of preventable blindness in the developing world.C. trachomatisinvades the epithelium of the conjunctiva and genital tract and replicates within an intracellular membrane-bound compartment termed the inclusion. To invade and replicate in mammalian cells,Chlamydiaremodels epithelial surfaces by reorganizing the cytoskeleton and cell–cell adhesions, reprograms membrane trafficking, and modulates cell signaling to dampen innate immune responses. If the infection ascends to the upper female genital tract, it can result in pelvic inflammatory disease and tissue scarring.C. trachomatisinfections are associated with infertility, ectopic pregnancies, the fibrotic disorder endometriosis, and potentially cancers of the cervix and uterus. Unfortunately, the molecular mechanisms by which this clinically important human pathogen subverts host cellular functions and causes disease have remained relatively poorly understood because of the dearth of molecular genetic tools to studyChlamydiaeand limitations of bothin vivoandin vitroinfection models. In this review, we discuss recent advances in the experimental molecular tool kit available to dissectC. trachomatisinfections with a special focus onChlamydia-induced epithelial barrier disruption by regulating the structure, function, and dynamics of epithelial cell–cell junctions.