Investigating the function of bacterial cytoskeletal elements in the division and growth of the FtsZ-less Chlamydia - Project Abstract: Investigating the Function of Bacterial Cytoskeletal Elements in the Division and Growth of the FtsZ-less Chlamydia Chlamydia is an obligate intracellular bacterial pathogen that causes a range of serious diseases in humans. In developed countries, Chlamydia trachomatis is the leading cause of bacterial sexually transmitted infections (STI). In developing countries, C. trachomatis is not only a significant cause of STI, but it is also responsible for the primary cause of infectious preventable blindness, trachoma. The major concern of chlamydial infections is that they are often asymptomatic and undiagnosed, which can lead to chronic sequelae. These include pelvic inflammatory disease, tubal factor infertility, and reactive arthritis for C. trachomatis. Chlamydial diseases remain a significant burden on health care systems around the world. In adapting to obligate intracellular growth, Chlamydia has significantly reduced its genome size and eliminated genes from various pathways as it relies on the host cell for its metabolic needs. One such “essential” gene that Chlamydia has eliminated is FtsZ, the central organizer of the division septum during binary fission. A major focus of the lab is to understand how Chlamydia divides. Previously, we have demonstrated that Chlamydia divides by an MreB-dependent polarized division mechanism that relies, in part, on the unique N-terminal domain of chlamydial MreB. This pathogen also alternates between different functional and morphological forms during its normal growth, also referred to as its developmental cycle. These observations, combined with its obligate intracellular dependence, make Chlamydia a difficult, but fascinating, organism with which to work. Nonetheless, recent development of genetic tools to mechanistically study chlamydiae has significantly enhanced our understanding of this pathogen. The current application goals are designed to leverage prior work investigating the function of chlamydial cytoskeletal elements. Goal 1: We will investigate how MreB is maintained at the division septum after its initial recruitment to a specific site on the bacterial surface as well as the contributions of various phospholipids to this process. We will also determine factors that contribute to how daughter cell outgrowth occurs during the budding process. Goal 2: We will investigate a novel bactofilin cytoskeletal element we identified that functions in maintaining cell size. We seek to understand its function in regulating cell size in Chlamydia by interrogating specific domains necessary for its effects and identifying interaction partners that contribute to cell size. We hypothesize that, given the absence of FtsZ in these organisms and their use of MreB in its place, the mechanisms of cell size control will be unique in these bacteria. Consequently, our results may lead to the identification of Chlamydia- unique targets for antimicrobial development. This will limit the impact of broad spectrum antibiotics on the microbiome during treatment of chlamydia infections. More fundamentally, findings from the proposed research will enhance our understanding of the evolutionary strategies bacteria employ to regulate a critical physiological function.
