Anti-adhesive prevention of Chlamydia trachomatis genital tract infection

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DESCRIPTION (provided by applicant): Sexually transmitted infections (STIs) have a huge impact on public health. Chlamydia trachomatis is the leading cause of bacterial sexually transmitted infections globally, and is the most prevalent sexually transmitted diseases in the United State, with an estimated 3 to 4 million cases in the United States per year. Infection of the mucosa results in cervicitis, endometritis, and salpingitis. The pathological consequences of untreated infections may result in severe reproductive tract disease including pelvic inflammatory disease (PID), ectopic pregnancy and infertility. Despite the high morbidity and cost burden, there are currently no effective vaccines. A promising alternative preventive approach is the use of topical microbicides that can be applied intravaginally in a gel, cream, or other formulation. Key to the development of effective strategies for preventing infection of this obligate intracellular pathogen is to prevent attachment and internalization. In this study, we propose to test the feasibility of using high mannose oligosaccharides as a novel topical microbicide for preventing C trachomatis infection. This approach is based on our studies demonstrating that the chlamydial glycan, a high mannose oligosaccharide, is key to attachment and infectivity by binding to the mannose receptor on host cells. Significantly, high mannose oligosaccharides or removal of the glycan inhibit infectivity in vitro in cell culture and in vivo in a mouse model of lung infection. Thus, we will test the hypothesis that high mannose oligosaccharides will be an effective anti-adhesive prevention method for C. trachomatis genital tract infection. This will be accomplished in vitro by determining the efficacy of high mannose oiigosaccharides in inhibiting infectivity of C. trachomatis genital serovars in vitro and in vivo in a mouse model of genital tract infection. PUBLIC HEALTH RELEVANCE: Chlamydia trachomatis is the leading cause of sexually transmitted infection in the US with severe outcomes in women including pelvic inflammatory disease, ectopic pregnancy and infertility. This proposal seeks to determine the feasibility of a novel anti-adhesive prevention method that could be used as a topical microbicide to prevent genital tract infection with this pathogen.