Impact of the vaginal microbiome on Chlamydia trachomatis acquisition

项目概要 每年有超过 1.3 亿新发沙眼衣原体感染，制定创新策略 预防这些感染是全球公共卫生的首要任务。许多前瞻性研究报告了 细菌性阴道病与沙眼衣原体感染风险增加之间的关联。然而，准确的 阴道细菌种类与沙眼衣原体易感性之间关联的性质，以及生物制剂 驱动这些关联的机制尚不清楚。体外研究的新数据表明 特定 BV 相关细菌产生的代谢物和酶影响泌尿生殖道沙眼衣原体 成长。然而，评估这种关系的体内研究数据很少。为了解决这个重要的 知识差距，我们提出了一种结合流行病学和实验室研究的多学科方法 评估阴道细菌及其代谢物对沙眼衣原体感染的影响。此次重新提交 将利用从参与蒙巴萨队列研究的女性收集的数据和样本，这是一项正在进行的 NIH- 赞助的开放队列研究。我们将使用广泛和广泛的方法进行巢式病例对照研究 定量 PCR 以确定 BV 相关物种的检测和浓度是否与 沙眼衣原体感染的风险增加（目标 1）。在目标 2 中，我们将测试作为项目一部分收集的阴道样本 病例对照研究评估沙眼衣原体使用的关键代谢物是否与增加 沙眼衣原体感染的风险。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 & 2 确定阴道代谢组功能变化的分类驱动因素，从而导致艰难梭菌增加。 沙眼易感性。拟议的研究代表了一种了解阴道如何 微生物组和代谢组介导沙眼衣原体易感性。拟议研究的结果将 确定增强沙眼衣原体易感性的关键目标并为创新衣原体的开发提供信息。 沙眼预防策略旨在破坏或消除细菌或代谢组学目标，从而促进 沙眼衣原体生长，从而减少沙眼衣原体感染。

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.