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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.

项目总结