Commensal control of C. difficile virulence

摘要：难辨梭状芽胞杆菌是伪膜性结肠炎的病原体，可引起实质性肠炎。 发病率、死亡率和近50亿美元/年的美国医疗成本。共生关系提供 通过基本作用机制对艰难梭菌感染的初级保护作用 仍然没有明确的定义。我们已经确定了能够提供长期生存的单个细菌种类 对抗高毒力的艰难梭菌和其他可能使感染恶化的物种。我们的 提议的目标将定义具体的共生活动和调节这些活动的共生基因 携带人-鼠复合体的小鼠对病原体的影响及其在体内的作用 微生物区系，用于开发明确的细菌治疗药物和生物标志物以预测 治疗成功了。

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.