Elucidation of Commensal Bacteria Mechanisms Required for Host Protection

项目摘要 动物中的微生物群提供了针对多种微生物病原体的感染的重要屏障， 编码抗感染和保护因子的重要储存库。确定抗感染和保护 来自肠道微生物群中有益细菌物种的因子，我们使用C.秀丽线虫作为模式生物， 评价针对人类肠道病原体的保护活性的单个细菌种类和特定因素 如鼠伤寒沙门氏菌。我们发现一种独特的分泌型肽聚糖水解酶佐贺， 屎肠球菌（人类和其他动物的肠道细菌）增强上皮屏障功能 足以保护C。elegans和S.鼠伤寒发病机制。这些令人兴奋的结果 提示佐贺在体内具有独特活性，可用于改善宿主屏障功能， 针对人类的肠道病原体和炎性肠病（IBD）。为了利用保护性的 活性的佐贺的治疗用途，我们建议确定的确切机制（S）的SagA介导的 在哺乳动物细胞和小鼠模型中的保护。我们对佐贺保护活性的发现， 令人兴奋的机会，了解有益的肠道细菌物种，如大肠杆菌的保护机制。 以及预防或治疗肠道微生物感染以及炎性肠病。

PROJECT SUMMARY Microbiota in animals provides an important barrier to infection against diverse microbial pathogens and encode an important reservoir of anti-infective and protective factors. To identify anti-infective and protective factors from beneficial bacterial species in gut microbiota, we used C. elegans as a model organism to evaluate individual bacteria species and specific factors for protective activity against human enteric pathogens such as Salmonella typhimurium. We discovered that a unique secreted peptidoglycan hydrolase, SagA, from Enteroccocus faecium (commensal bacteria in humans and other animals) enhanced epithelial barrier function and was sufficient to protect C. elegans and mice from S. typhimurium pathogenesis. These exciting results suggest that SagA has unique activity in vivo and may be used to improve host barrier function to protect against enteric pathogens and inflammatory bowl diseases (IBDs) in humans. To harness the protective activity of SagA for therapeutic use, we propose to determine the precise mechanism(s) of SagA-mediated protection in mammalian cells and mouse models. Our discovery of SagA protective activity provides an exciting opportunity to understand the protective mechanism of beneficial gut bacterial species such as E. faecium and to prevent or treat enteric microbial infections as well as inflammatory bowl disorders.