University of Washington Sexually Transmitted Infections Cooperative Research Cen

描述（由申请人提供）：我们的目标是在华盛顿大学（UW）建立一个性传播感染（STI）合作研究中心，以调查人类生殖器微生物组与导致STI相关发病率的综合征和病原体之间的相互作用。我们将应用我们的密集采样和生殖器微生物组的强大表征的创新方法，对两个高风险人群中STI病原体，细菌群落和综合征表现之间关键相互作用的潜在生物学机制进行前沿调查：育龄妇女和与男性发生性关系的男性（MSM）。重要的是，我们的工作将超越传统的编目和关联研究，这些研究是早期微生物组研究的特征，通过定义微生物群落变化的决定因素和机制，包括生殖器细菌与STI病原体的相互作用，常见综合征的宿主反应的触发因素，以及当地环境因素;这反过来将为预防和管理提供新的方法。通过强大和经验丰富的核心，我们将为四个相互关联的研究项目提供科学和领导基础设施支持，为新的研究人员提供发展研究项目奖，以及CRCs和NIH之间的互动。研究项目旨在（1）通过每日肛门和阴道采样检测HSV、Nugent评分和BV相关细菌（BVAB），确定生殖器HSV-2脱落是否通过生殖器炎症增加而增加BV风险，以定义HSV-2脱落与HSV-2和频繁BV女性阴道微生物组变化之间的时间关系。(2)使用一套综合的临床、实验室和建模研究，通过自我收集的每日阴道拭子，确定BV发展和持续所需的生化、微生物和生物膜阈值水平，以测量微生物变化期间（包括月经、BV事件和抗生素治疗）的定量细菌和生化水平，以及使用专门的体外系统测量不同多微生物和生物化学条件下的细菌生长和竞争动力学的验证。(3)定义男性尿道微生物组，因为它与性行为有关，特别是在MSM中，以及它与尿道炎的关系，使用16 S rRNA基因PCR和测序，以确定预测标准抗生素治疗后NGU复发或持续的细菌群落或物种。(4)描述阴道微生物组和阴道环（CVR）中递送的激素避孕药之间的相互作用，局部免疫和阴道生态失调作为主要结局，分析CVR对保护性乳杆菌属优势微生物组的发展和维持的贡献。

DESCRIPTION (provided by applicant): Our objective is to establish a Sexually Transmitted Infection (STI) Cooperative Research Center at the University of Washington (UW) to investigate interactions between the human genital microbiome and syndromes and pathogens that contribute to STI-related morbidity. We will apply our innovative approach of intensive sampling and robust characterization of the genital microbiome to cutting-edge investigation of the underlying biological mechanisms of key interactions between STI pathogens, bacterial communities, and syndromic presentations in two high-risk populations: reproductive-age women and men who have sex with men (MSM). Importantly, our work will go beyond the traditional cataloguing and association studies that have characterized early microbiome research by defining determinants of, and mechanisms underlying, shifts in microbial communities, including interactions of genital bacteria with STI pathogens, triggers of host responses that characterize common syndromes, and local environmental factors; this will in turn inform new approaches to prevention and management. Through robust and experienced Cores, we will provide scientific and leadership infrastructure support for four inter-related Research Projects, Developmental Research Project awards for new investigators, and interactions among CRCs and with NIH. The Research Projects address (1) Determine whether genital HSV-2 shedding increases risk of BV via increased genital inflammation through daily anogenital and vaginal sampling for detection of HSV, Nugent score and BV-associated bacteria (BVAB) to define the temporal relationship between HSV-2 shedding and shifts in the vaginal microbiome in women with HSV-2 and frequent BV. (2) Identify biochemical, microbial and biofilm threshold levels necessary for the development and persistence of BV using an integrated set of clinical, laboratory and modeling studies through self-collected daily vaginal swabs to measure quantitative bacterial and biochemical levels during periods of microbial shifts, including menses, incident BV, and antibiotic treatment, and validation using specialized in vitro systems to measure bacterial growth and competition dynamics under different polymicrobial and biochemical conditions. (3) Define the urethral microbiome in men as it relates to sexual practices, particularly in MSM, and its relationship to urethritis with 16S rRNA gene PCR and sequencing, to identify bacterial communities or species that predict NGU recurrence or persistence after standard antibiotic therapy. (4) Characterize interactions between the vaginal microbiome and hormonal contraceptive delivered in a vaginal ring (CVR), with local immunity and vaginal dysbiosis as primary outcomes, with analysis of the contribution of the CVR to development and maintenance of a protective Lactobacillus-dominant microbiome.