Understanding the Cell Forms That Underlie the Chlamydial Developmental Cycle

Chlamydia trachomatis is a bacteria that relies upon a developmental cycle consisting of three distinct cell forms: reticulate bodies (RBs), intermediate bodies (IBs), and elementary bodies (EBs). RBs replicate within host cells but are not infectious. EBs are infectious but cannot replicate. IBs are transitional forms from RB to EB. Developmental cycle completion is central to chlamydial pathogenesis in that C. trachomatis are obligate intracellular parasites of eukaryotic cells. Infection of this specific genus of Chlamydia can cause blinding trachoma as well as STIs with the potential to cause pelvic inflammatory disease and infertility. The regulation and mechanisms of these cell forms are currently poorly understood. Preliminary and published data indicate four stages of the cycle, but understanding cellular contributions to the developmental cycle and pathogenesis can be difficult due to mixed cell environments of chlamydial inclusions. Therefore, this project will focus on understanding the regulation of gene expression in these early populations, and the impact of regulation on the infectious cycle. We will develop a CRISPRi knockdown screen to assess the role of essential genes on cell type regulation, and then investigate the role of cell type-specific expression.