Title: The Role of Chlamydia trachomatis Inc Proteins in Modulating the Immune Response Chlamydia trachomatis is the most commonly reported bacterial infection in the United States and the leading cause of sexually transmitted infections worldwide with approximately 90 million new cases reported annually. Infection by C. trachomatis can lead to severe medical complications in women including pelvic inflammatory disease. Despite these concerns there are fundamental gaps in our understanding of Chlamydia pathogenesis, particularly with regards to the host immune response and mechanisms used to manipulate host proteins for intracellular survival and dissemination. The long term goal of our research is to determine the role of two chlamydial inclusion membrane proteins during C. trachomatis infection and the subsequent immune response. Based on our preliminary as well as our recently published data, the central hypothesis is that Chlamydial Inc proteins, CT226 and CT228, are important factors for driving host immune responses. With the latest innovative genetic tools and transformation methods, C. trachomatis is no longer genetically intractable. Thus, we propose to genetically mutate and complement CT226 as we have previously accomplished with CT228. The CT226 deletion mutant will be assessed for loss of specific host cell protein recruitment, infectious progeny formation and any defects in cell culture. Both the CT226 deletion mutant and previously described CT228 deletion mutant will be assessed in the murine infection model. These studies will determine the role of both Chlamydial Inc proteins CT226 and CT228 in Chlamydia pathogenesis. As such, the proposed research is critical to understanding the role inclusion membrane proteins have in host immune response during C. trachomatis infections and will address a key fundamental gap in Chlamydia pathogenesis.
/relevance Chlamydia trachomatis is a well-known sexually transmitted bacteria that causes millions of infections in the United States and worldwide yearly. This pathogen is very versatile and affects the immune response of infected cells. This research will increase our knowledge on how our bodies mount an immune response against these bacteria.