Genetic Dissection of Chlamydia spp. Determinants of Tissue Tropism, Stress Response and Nutrient Acquisition

Abstract

Chlamydia trachomatis (CT) is an obligate intracellular bacterium that transitions between two distinct morphological forms during its complex developmental cycle. During the intracellular portion of its developmental cycle, CT multiplies, evades host immunity, and acquires nutrients. CT is the causative agent of chlamydia, the most common bacterial sexually transmitted disease in the US. CT infection sometimes elicits a robust host immune response which drives most chlamydia-associated pathology. Chlamydia outcomes include urethritis in men and women, cervicitis in women, as well as severe complications including pelvic inflammatory disease and ectopic pregnancies in women and epididymitis in men. Sexually transmitted CT strains can also colonize multiple tissues in their hosts, apart from urogenital organs. For example, CT can infect cells of the gastrointestinal (GI) tract. Unlike urogenital infection, GI CT usually does not elicit inflammatory pathology. My goal was to identify genes that are central to CT pathogenesis. In one project, I characterized CTL0225, and showed that it is an amino acid transporter that helps CT acquire essential nutrients from the host cell. In another project, I identified a protease that helps CT survive stress, such as exposure to high temperature. I also found evidence that this protease plays a crucial role in the transition between morphological forms during CT development. Finally, I identified several novel genes that may contribute to CT tissue tropism using a genetic screen. Overall, I have identified and characterized several new CT factors that mediate the survival and virulence of this important pathogen.