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.

翻译后摘要：艰难梭菌，伪膜性结肠炎的病因，造成实质性的 发病率、死亡率和近50亿美元/年的美国医疗保健成本。Commensals提供 主要保护C。艰难的感染，虽然潜在的作用机制 仍然不明确。我们已经确定了能提供长期存活的单个细菌物种 对C.艰难的菌株，和其他物种，可以使感染恶化。我们 提出的目标将定义特定的神经活动和介导这些活动的神经基因。 对病原体的影响，并在体内测试它们的功能，在小鼠携带小鼠vs人复合物 微生物群，用于开发确定的细菌治疗药物和生物标志物来预测 成功的治疗