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：梭状芽胞杆菌艰难梭菌（伪膜结肠炎的病因）导致实质性 美国医疗保健费用的发病率，死亡率和接近50亿美元/年。共生提供 通过基本的作用机理，对艰难梭菌感染的主要保护 保持不确定。我们已经确定了提供长期生存的单个细菌物种 针对有毒的艰难梭菌菌株和其他可能使感染恶化的物种。我们的 提出的目标将定义特定的共生活动和介导的共生基因 在携带小鼠与人类复合物的小鼠中对病原体的影响并在体内测试其功能 微生物群，目的是开发定义的细菌疗法和生物标志物来预测 成功的治疗。