Pathogenesis of Bacterial Vaginosis in Women Who Have Sex with Women

与女性发生性关系的女性细菌性阴道病的发病机制

• 批准号: 8850392
• 负责人: Christina A Muzny
• 金额: $ 16.83万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-06-01 至 2019-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8850392
• 关键词: African American; Anaerobic Bacteria; Anal Sex; Appearance; Atopobium vaginae; Award; Bacteria; Bacterial Vaginosis; Bacteroides; Behavior; Behavioral; Bioinformatics; Clinical Microbiology; Clinical Research; Complex; Conflict (Psychology); Data; Development; Diagnosis; Diagnostic; Entropy; Epidemiology; Etiology; Event; Exposure to; Female; Gardnerella vaginalis; Genes; Gram' s stain; HIV; Health; Heterosexuals; Hydrogen Peroxide; Infection; Lactobacillus; Menstruation; Mentored Patient-Oriented Research Career Development Award; Metabolic Pathway; Methods; Microbial Biofilms; Mobiluncus; Modeling; Molecular; Mouth Diseases; Oral; Organism; Oxidation-Reduction; Pathogenesis; Pelvic Inflammatory Disease; Peptostreptococcus; Population; Premature Birth; Prevalence; Prevention; Prevotella; Race; Relative (related person); Research; Research Personnel; Risk; Risk Factors; Sampling; Sex Behavior; Sexual Partners; Sexually Transmitted Diseases; Swab; Syndrome; Taxon; Techniques; Testing; Time; Toy; Training; Translational Research; United States; Unsafe Sex; Vagina; Vaginal Discharge; Vaginal Douching; Woman; Women' s Group; adverse outcome; base; design; diaries; experience; male; men; microbiome; microorganism; pyrosequencing; rRNA Genes; routine Bacterial stain; sex; sexually active; skills; transmission process; women who have sex with women

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.

描述（由申请人提供）：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%。它与不良后果相关，包括早产、盆腔炎和性传播感染（STI）（包括艾滋病毒）风险增加。 BV 代表阴道微生物群从以乳杆菌为主的菌种向兼性（阴道加德纳菌；GV）和严格厌氧菌的转变。 BV 在与女性发生性关系 (WSW) 的女性中非常常见，并且被假设为 STI。然而，BV 的发病机制仍不清楚。关于 BV 是否由获得 GV 作为“创始”生物体而导致，随后导致与 BV 相关的阴道微生物群发生复杂变化，BV 是否作为多种微生物群落传播，[或者 BV 是否由行为引起，仍存在争议。影响阴道菌群的因素]与严格厌氧菌（即其他 BV 相关细菌：BVAB）不同，GV 作为一种兼性厌氧菌，可能能够耐受健康阴道微生物组的高氧化还原 (redox) 电位。与引发口腔疾病的兼性厌氧菌类似，GV 可能会在阴道微生物组中产生较低的氧化还原电位，从而导致乳酸杆菌显着减少和其他 BVAB（通常可能以非常低的浓度存在）增加，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，因为没有与这种感染相当的男性，而且非裔美国人种族是 BV 的危险因素]。我推测 AAWSW 中 GV 的性接触是导致与 BV 相关的复杂阴道菌群的刺激事件。为了检验这个假设，我提出了以下独立但相互关联的目标。 [目标1：使用独立于培养的分子方法来确定性活跃的 AAWSW 中最终导致 BV 的微生物事件的顺序。我假设，在其他 BVAB 丰度增加之前，发生 BV 的女性中 GV 的出现及其相对丰度会增加。] [目标 2：确定特定 GV 寡型是否与性活跃 AAWSW 中 BV 的发展相关。我假设 GV 寡型在 BV 发展方面的致病潜力有所不同，因为存在相互矛盾的观察结果，即 GV 可能存在于“正常”女性和患有 BV 的女性中。] 这项指导性的、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与培养无关的分子诊断、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。该奖项创造的机会将使我成为一名独立的转化研究调查员，具备道德地、准确地回答与 BV 发病机制相关的重要科学问题所需的技能。确定 BV 的确切病原体对于适当治疗和预防不良后果至关重要。