Pathogenesis of Bacterial Vaginosis in Women Who Have Sex with Women

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DESCRIPTION (provided by applicant): Bacterial vaginosis (BV) is the most common vaginal infection in the United States, with an estimated prevalence of 30%. It is associated with adverse outcomes including preterm birth, pelvic inflammatory disease, and increased risk for sexually transmitted infections (STIs), including HIV. BV represents a shift in the vaginal microbiota from Lactobacillus-predominate species to facultative (Gardnerella vaginalis; GV) and strict anaerobic bacteria. BV is very common among women who have sex with women (WSW) and it is hypothesized to be an STI. However, the pathogenesis of BV remains unclear. It remains controversial as to whether BV results from acquisition of GV as the "founder" organism which subsequently leads to the complex changes in the vaginal microbiota associated with BV, whether BV is transmitted as a polymicrobial consortium, [or whether BV is caused by behavior factors influencing the vaginal microbiota]. GV, as a facultative anaerobe, may be able to tolerate the high oxidation-reduction (redox) potential of a healthy vaginal microbiome, unlike strict anaerobes (i.e. other BV-associated bacteria: BVAB). Similar to facultative anaerobes involved in the initiation of oral disease, it is possible that GV creates a lower redox potential in the vaginal microbiome which causes a marked decrease in lactobacilli and an increase in other BVAB (which may normally be present in very low concentrations), leading to the BV syndrome. WSW, [particularly African American WSW (AAWSW), are a unique population in which to study BV pathogenesis as there is no male equivalent to this infection and African American race is a risk factor for BV]. I hypothesize that sexual exposure to GV among AAWSW is the inciting event leading to the complex vaginal flora associated with BV. To test this hypothesis, I propose the following independent but inter-related aims. [Aim1: Use cultivation-independent molecular methods to determine the sequence of microbiological events culminating in BV among sexually active AAWSW. I hypothesize that the appearance of GV and its relative abundance will increase in women with incident BV prior to increases in the abundance of other BVAB.] [Aim 2: Determine if specific GV oligotypes are associated with the development of BV among sexually active AAWSW. I hypothesize that GV oligotypes differ in their pathogenic potential with regards to the development of BV given the conflicting observation that GV can be present in both "normal" women and women with BV.] This mentored, patient oriented research career development award and research aims are designed to provide me with advanced training in cultivation-independent molecular diagnostics, bioinformatics techniques, clinical microbiology, and the fundamentals of clinical research. The opportunities created by this award will allow me to become an independent translational research investigator with the skills necessary to ethically and accurately answer important scientific questions related to BV pathogenesis. Determining the exact causative agent(s) of BV is vital for the appropriate treatment and prevention of adverse outcomes.