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，以研究人类生殖器微生物群与导致STI相关发病率的综合征和病原体之间的相互作用。我们将运用我们的创新方法，即密集采样和生殖器微生物组的强大特征，对两个高危人群：育龄妇女和男男性行为者（MSM）中性传播感染病原体、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研究。重要的是，我们的工作将超越传统的分类和关联研究，这些研究是早期微生物组研究的特点，通过定义微生物群落变化的决定因素和潜在机制，包括生殖器细菌与性传播感染病原体的相互作用，表征常见综合征的宿主反应的触发因素，以及当地环境因素；这将反过来为预防和管理的新方法提供信息。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，为新研究者提供发展研究项目奖励，以及crc之间和NIH之间的互动。研究项目(1)通过每日肛门生殖器和阴道取样检测HSV、Nugent评分和BV相关细菌（BVAB），确定生殖器HSV-2脱落是否通过增加生殖器炎症增加BV的风险，以确定HSV-2脱落与阴道微生物群变化之间的时间关系。(2)通过综合临床、实验室和模型研究，确定细菌性阴道炎发展和持续所需的生化、微生物和生物膜阈值水平，通过自我收集的每日阴道拭子来测量微生物变化期间的定量细菌和生化水平，包括月经、事件细菌性阴道炎和抗生素治疗；并使用专门的体外系统验证在不同的多微生物和生化条件下测量细菌生长和竞争动态。(3)通过16S rRNA基因PCR和测序确定男性尿道微生物群，因为它与性行为有关，特别是在男男性行为中，以及它与尿道炎的关系，以确定细菌群落或物种，预测NGU在标准抗生素治疗后复发或持续。(4)描述阴道微生物群与阴道环内激素避孕药（CVR）之间的相互作用，以局部免疫和阴道生态失调为主要结果，并分析CVR对保护性乳酸杆菌优势微生物群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.