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

• 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
• 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

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.

项目摘要 每年有超过1.3亿个新衣原体沙眼感染，创新策略的发展 为了防止这些感染是全球公共卫生的重点。许多前瞻性研究报告了 细菌性阴道病与沙眼梭状芽孢杆菌获取的风险增加之间的关联。但是，确切的 阴道细菌物种与沙眼梭状芽胞庭易感性与生物学之间的关联性质 推动这些关联的机制尚不清楚。来自体外研究的新兴数据表明 由特定BV相关细菌产生的代谢物和酶会影响泌尿生殖器C.沙眼 生长。但是，评估这种关系的体内研究数据很少。解决这个重要的 知识差距，我们提出了一种多学科方法，将流行病学和实验室研究结合在一起 评估阴道细菌及其代谢产物对沙眼曲霉的影响。此重新提交 将利用参加蒙巴萨队列研究的妇女收集的数据和样本，这是一项正在进行的NIH- 赞助的开放队列研究。我们将使用宽范围和 定量PCR确定BV相关物种的检测和浓度是否与 增加了沙眼梭状疱疹感染的风险（AIM 1）。在AIM 2中，我们将测试收集的阴道样本 病例对照研究，以评估C.沙眼使用的关键代谢产物是否与增加有关 沙眼梭状芽胞庭感染的风险。在AIM 3中，我们将使用系统生物学方法来整合目标1 ＆2确定阴道代谢组中功能转移的分类驱动因素导致C的增加。 气管瘤易感性。拟议的研究代表了一种新的方法，可以理解阴道 微生物组和代谢组介导了沙眼炎的易感性。拟议研究的发现将 确定增强梭状瘤易感性并为创新C.开发的关键目标。 试图破坏或消除有助于促进细菌或代谢组的预防气管预防策略 C.沙眼生长，从而减少了沙眼梭状芽胞盘感染。