Impact of the vaginal microbiome on Chlamydia trachomatis acquisition

项目总结 随着每年超过1.3亿新的沙眼衣原体感染，创新战略的制定 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， 细菌性阴道病与沙眼衣原体获得性风险增加之间的关系。然而，准确的 阴道细菌种类与沙眼衣原体敏感性的关系的性质，以及生物学 推动这些关联的机制还没有被很好地理解。来自体外研究的新数据表明 由特定的BV相关细菌产生的代谢产物和酶影响泌尿生殖道沙眼衣原体 成长。然而，来自体内研究评估这种关系的数据很少。要解决这一重要问题 知识鸿沟，我们提出了一种多学科方法，将流行病学和实验室研究相结合，以 评估阴道细菌及其代谢物对沙眼衣原体感染的影响。这次重新提交 将利用从参与蒙巴萨队列研究的女性那里收集的数据和样本，这是一项正在进行的NIH- 赞助的开放式队列研究。我们将进行一项嵌套病例对照研究，使用广泛的和 定量聚合酶链式反应确定BV相关物种的检测和浓度是否与 增加沙眼衣原体感染风险(目标1)。在目标2中，我们将检测采集的阴道样本，作为 评价沙眼衣原体使用的关键代谢物是否与 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来自目标1的数据 -2确定导致C升高的阴道代谢组功能变化的分类学驱动因素。 沙眼衣原体敏感性。提出的研究代表了一种新的方法来理解阴道是如何 微生物组和代谢组介导沙眼衣原体的敏感性。拟议中的研究结果将 确定提高沙眼衣原体敏感性的关键靶点，并为创新的C。 寻求破坏或消除细菌或代谢组学目标的沙眼衣原体预防策略 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.