Pathogenesis of Bacterial Vaginosis in Women Who Have Sex with Women

描述(申请人提供)：细菌性阴道病(BV)是美国最常见的阴道感染，估计患病率为30%。它与不良后果有关，包括早产、盆腔炎和包括艾滋病毒在内的性传播感染(STI)风险增加。BV代表着阴道微生物群从以乳杆菌为主的种类转变为兼性(GV)和严格的厌氧细菌。BV在与女性发生性行为的女性中非常常见，并被假设为性传播感染。然而，BV的发病机制尚不清楚。BV是否是由于获得GV作为“创始”生物体而导致与BV相关的阴道微生物区系的复杂变化，BV是否作为多菌群传播，或者BV是否是由影响阴道微生物区系的行为因素引起的，目前仍存在争议。GV作为一种兼性厌氧菌，与严格的厌氧菌(即其他BV相关细菌：BVAB)不同，它可能能够耐受健康的阴道微生物群的高氧化还原(氧化还原)潜力。与引起口腔疾病的兼性厌氧菌相似，GV可能在阴道微生物群中产生较低的氧化还原电位，导致乳酸杆菌显著减少，其他BVAB(通常存在于极低浓度)增加，从而导致BV综合征。WSW，特别是非裔美国人WSW(AAWSW)，是研究BV发病机制的独特人群，因为没有男性等同于这种感染，而非裔美国人是BV的危险因素]。我推测，在AAWW人群中，性接触GV是导致与BV相关的复杂阴道菌群的激发事件。为了验证这一假设，我提出了以下独立但相互关联的目标。目的：使用非培养依赖的分子方法来确定在性行为活跃的AAWSW中最终导致BV的微生物事件的序列。我推测，在发生BV的妇女中，GV的出现及其相对丰度将先于其他BVAB的丰度增加。]目的2：确定特定的GV亚型是否与性行为活跃的AAWSW中BV的发生有关。我假设，GV寡型在BV的发展方面具有不同的致病潜力，因为相互矛盾的观察表明，GV可能存在于“正常”妇女和BV妇女中。]这个有指导的、以患者为导向的研究职业发展奖和研究目标旨在为我提供独立于培养的分子诊断学、生物信息学技术、临床微生物学和临床研究基础方面的高级培训。这个奖项创造的机会将使我成为一名独立的翻译研究调查员，拥有必要的技能，从伦理上和准确地回答与BV发病机制相关的重要科学问题。确定BV的确切病原体(S)对于适当的治疗和预防不良后果至关重要。

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.