Molecular Analysis of the Chlamydia Trachomatis Virulence Factor Tarp

C. trachomatis represent a medically significant agent of human disease. A well]established approach using intravaginal or transcervical infection of female mice has been used to model genital infection outcomes. Our collaborative project has resulted in the generation of a mutant Chlamydia strain lacking the suspected virulence factor TarP. Work proposed at the University of Kentucky is contained within Aim3 of the proposal and is focused on using the murine infection model to elucidate deficiencies in pathogenesis manifested by the mutant strain. Groups of female mice will be challenged with chlamydial strains to elucidate infectivity defects. Strains will include WT, mutant and complemented C. trachomatis. Initial studies will enumerate shed bacteria over time to assess the degree of infectivity. Attenuated strains will then be used in the transcervical infection model to examine more refined characteristics that govern disease outcome. These include the ability of chlamydiae to colonize the upper genital tract and cause pathology indicative of Chlamydia]mediated disease. At the end of the study, the role of TarP as well as individual functional subdomains in infection will be elucidated. Dr. Fieldsf lab routinely employs the murine infection model and will perform all the studies proposed in Aim 3.