Impact of the vaginal microbiome on Chlamydia trachomatis acquisition

项目摘要 每年有超过1.3亿新的沙眼衣原体感染， 预防这些感染是全球公共卫生的优先事项。一些前瞻性研究报告称， 细菌性阴道病与C.沙眼获得性然而，精确 阴道细菌种类和C.沙眼易感性，以及生物学 驱动这些关联的机制尚不清楚。来自体外研究的新数据表明 由特定BV相关细菌产生的代谢物和酶影响泌尿生殖道C。沙眼衣原体 增长然而，评估这种关系的体内研究数据很少。处理这一重要 知识差距，我们提出了一个多学科的方法，结合流行病学和实验室研究， 评估阴道细菌及其代谢产物对C.沙眼获得性这次重新提交 将利用从参与蒙巴萨队列研究的妇女中收集的数据和样本，这是一项正在进行的NIH- 申办的开放队列研究。我们将进行一项巢式病例对照研究， 定量PCR，以确定BV相关物质的检出和浓度是否与 C的风险增加。沙眼感染（目的1）。在目标2中，我们将测试作为 病例对照研究，以评估C.沙眼与 C的风险。沙眼感染在目标3中，我们将使用系统生物学方法来整合目标1中的数据 和2，以确定导致C增加的阴道代谢组中的功能转变的分类学驱动因素。 沙眼易感性这些研究提出了一种新的方法来了解阴道 微生物组和代谢组介导C.沙眼易感性拟议研究的结果将 确定增强C的关键目标。沙眼衣原体易感性及创新性C. 沙眼预防策略，寻求破坏或消除细菌或代谢组学目标， C.沙眼衣原体生长，从而减少C.沙眼感染

PROJECT SUMMARY With over 130 million new Chlamydia trachomatis infections each year, the development of innovative strategies to prevent these infections is a global public health priority. A number of prospective studies have reported an association between bacterial vaginosis and increased risk of C. trachomatis acquisition. However, the precise nature of the association between vaginal bacterial species and C. trachomatis susceptibility, and the biologic mechanisms driving these associations, are not well understood. Emerging data from in vitro studies suggest that metabolites and enzymes produced by specific BV-associated bacteria impact urogenital C. trachomatis growth. However, data from in vivo studies assessing this relationship are sparse. To address this important knowledge gap, we propose a multidisciplinary approach that combines epidemiologic and laboratory studies to assess the impact of vaginal bacteria, and their metabolites, on C. trachomatis acquisition. This resubmission will utilize data and samples collected from women participating in the Mombasa Cohort study, an ongoing NIH- sponsored open cohort study. We will conduct a nested case-control study using both broad-range and quantitative PCR to determine if detection and concentrations of BV-associated species are associated with increased risk of C. trachomatis infection (Aim 1). In Aim 2, we will test vaginal samples collected as part of the case-control study to evaluate whether key metabolites used by C. trachomatis are associated with increased risk of C. trachomatis infection. In Aim 3, we will use a systems biology approach to integrate data from Aims 1 & 2 to identify taxonomic drivers of functional shifts in the vaginal metabolome that lead to increased C. trachomatis susceptibility. The proposed studies represent a novel approach to understanding how the vaginal microbiome and metabolome mediate C. trachomatis susceptibility. Findings from the proposed research will identify critical targets that enhance C. trachomatis susceptibility and inform development of innovative C. trachomatis prevention strategies that seek to disrupt or eliminate bacterial or metabolomics targets that facilitate C. trachomatis growth, thus reducing C. trachomatis infection.