Cellular and molecular studies of the human pathogen Chlamydia trachomatis

Chlamydia trachomatis is a gram-negative bacterium and human pathogen responsible for the most prevalent sexually transmitted infection in the world. Epidemiologic studies indicate that the number of new C. trachomatis infections reported in the US likely approaches as much as 0.5 per a population of 100 every year. This, when paired with the fact that all current forms of treatment for C. trachomatis infections have unintended side effects including harm to gut and vaginal microbiota, has compelled many biologists to look to further research on C. trachomatis in hopes of developing new antichlamydial agents. In this thesis, I review several projects involving C. trachomatis that provide a framework for understanding both the growth and the developmental cycle of C. trachomatis. Through a mixture of in-depth proteomics, transcriptomics, and in vivo assays, I present five overall conclusions: (i) Lactobacilli-derived lactic acid, at concentrations that are physiological in the cervicovaginal lumen, can disrupt the outer membrane complex of and inactivate C. trachomatis; (ii) immunoprecipitation of chlamydial elementary bodies (EBs) using an antibody against a cell-surface protein of C. trachomatis is not an efficient method for purifying the bacterium; (iii) the growth of bacterial species that share significant sequence identity may not always be similar in media containing the same sera; (iv) the Chlamydia-specific transcription factor, GrgA, can stimulate transcription from promoters recognized by two different σ factors of C. trachomatis and has differential affinity for these two σ factors; (v) GrgA may associate with multiple subunits of the chlamydial RNA polymerase and, considering its role in transcription regulation and its specificity, may prove to be an excellent target for novel therapeutic agents against C. trachomatis.M.S.Includes bibliographical referencesby Malhar Desa