Impact of the vaginal microbiome on Chlamydia trachomatis acquisition

阴道微生物组对沙眼衣原体感染的影响

基本信息

批准号：
10541862
负责人：
Raymond Scott McClelland
金额：
$ 64.05万
依托单位：
UNIVERSITY OF WASHINGTON
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-01-14 至 2024-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10541862
关键词：
Address Automobile Driving Bacteria Bacterial Vaginosis Biological Biological Assay Biological Markers Case/Control Studies Censuses Chlamydia Infections Chlamydia trachomatis Cohort Studies Communities Computing Methodologies Data Detection Development Diagnosis Ectopic Pregnancy Enzymes Epidemiology Fusobacterium Gene Family Genitourinary system Growth HIV Infections HIV-1 Health High Prevalence High Risk Woman High-Throughput Nucleotide Sequencing Host Defense Human In Vitro Indoles Infection Infection prevention Infertility Intervention Knowledge Laboratories Laboratory Study Link Longitudinal Studies Mediating Metabolism Metagenomics Methods Molecular Nature Nested Case-Control Study Outcome Pelvic Inflammatory Disease Porphyromonas Positioning Attribute Predisposition Prevalence Prevention Prevention strategy Prevotella Process Prospective Studies Public Health Reporting Reproductive Health Research Risk Risk Factors Role Sampling Sexually Transmitted Diseases Shotguns Systems Biology Taxonomy Testing Tryptophan United States United States National Institutes of Health Vagina Variant Visit Woman aged bacterial community case control cohort data integration design epidemiology study improved in vivo innovation interdisciplinary approach metabolic profile metabolome metabolomics metagenome neonatal infection novel strategies public health priorities rRNA Genes reproductive reproductive tract screening sexual risk behavior vaginal fluid vaginal microbiome

项目摘要

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.

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优先事项。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生长。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新的方法来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。