In Search of a Mechanistic Link between Chlamydia trachomatis-Induced Cellular Pathophysiology and Oncogenesis

Centrosome duplication and cell cycle progression are essential cellular processes that must be tightly controlled to ensure cellular integrity. Despite their complex regulatory mechanisms, microbial pathogens have evolved sophisticated strategies to co-opt these processes to promote infection. While misregulation of these processes can greatly benefit the pathogen, the consequences to the host cell can be devastating. During infection, the obligate intracellular pathogen Chlamydia trachomatis induces gross cellular abnormalities, including supernumerary centrosomes, multipolar spindles, and defects in cytokinesis. While these observations were made over 15 years ago, identification of the bacterial factors responsible has been elusive due to the genetic intractability of Chlamydia. Recent advances in techniques of genetic manipulation now allows for the direct linking of bacterial virulence factors to manipulation of centrosome duplication and cell cycle progression. In this review, we discuss the impact, both immediate and downstream, of C. trachomatis infection on the host cell cycle regulatory apparatus and centrosome replication. We highlight links between C. trachomatis infection and cervical and ovarian cancers and speculate whether perturbations of the cell cycle and centrosome are sufficient to initiate cellular transformation. We also explore the biological mechanisms employed by Inc proteins and other secreted effector proteins implicated in the perturbation of these host cell pathways. Future work is needed to better understand the nuances of each effector's mechanism and their collective impact on Chlamydia's ability to induce host cellular abnormalities.