Commensal control of C. difficile virulence

艰难梭菌毒力的共生控制

• 批准号: 10334540
• 负责人: LYNN BRY
• 金额: $ 67.37万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-02-01 至 2026-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10334540
• 关键词: Amino Acids; Antibiotics; Bile Acids; Biological Markers; Biomass; Butyrates; Carbohydrates; Carbon; Clindamycin; Clostridium; Clostridium bifermentans; Clostridium difficile; Coenzyme A; Colon; Complex; Disease; Environment; Etiology; Fermentation; Genes; Genetic; Germination; Glycine; Growth; Health Care Costs; Human; Hydro-Lyases; Hydrolase; In Vitro; Individual; Infection; Infection prevention; Intervention Studies; Knowledge; Leucine; Mediating; Metabolic; Metabolic Pathway; Metabolism; Microbe; Morbidity - disease rate; Mus; Nutrient; Oral; Outcome; Oxidants; Oxidoreductase; Pathway interactions; Patients; Population; Production; Proline; Pseudomembranous Colitis; Reproduction spores; Resources; Source; System; Testing; Tissues; Toxic Megacolon; Toxin; Virulence; Virulent; Weight Gain; bile salts; biological adaptation to stress; fecal transplantation; human microbiota; in vivo; metabolomics; microbiota; mortality; mutant; pathogen; prevent; programs; transcriptomics

Abstract: Clostridioides difficile, the etiology of pseudomembranous colitis, causes substantive morbidity, mortality and close to $5 billion/year in US healthcare costs. Commensals provide primary protection against C. difficile infections though the underlying mechanisms of action remain ill-defined. We have identified individual bacterial species that provide long-term survival against virulent C. difficile strains, and other species that can make the infection worse. Our proposed aims will define specific commensal activities and commensal genes mediating these effects on the pathogen, and test their functions in vivo, in mice carrying mouse vs human complex microbiota, for the purposes of developing defined bacteriotherapeutics and biomarkers to predict successful therapy.

摘要： 艰难梭菌是伪膜性结肠炎的病因，可引起实质性的并发症。 发病率、死亡率以及美国每年近 50 亿美元的医疗费用。共生体提供 通过潜在的作用机制对艰难梭菌感染提供主要保护 仍然不明确。我们已经确定了能够长期生存的单个细菌种类 对抗强毒力的艰难梭菌菌株和其他可能使感染恶化的物种。我们的 拟议的目标将定义具体的共生活动和介导这些活动的共生基因 对病原体的影响，并在携带小鼠与人类复合物的小鼠体内测试其功能 微生物群，用于开发明确的细菌治疗剂和生物标志物来预测 成功的治疗。