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Elucidation of Commensal Bacteria Mechanisms Required for Host Protection

阐明宿主保护所需的共生细菌机制

基本信息

批准号：
9894505
负责人：
Howard C Hang
金额：
$ 4.27万
依托单位：
ROCKEFELLER UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-01-01 至 2021-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9894505
关键词：
Acetylmuramyl-Alanyl-Isoglutamine Animal Model Animals Anti-Infective Agents Antibiotics Bacteria Bacterial Infections Biochemical Biochemical Genetics Caenorhabditis elegans Cell Culture Techniques Cell model Chemicals Collaborations Disease Enteral Enterococcus faecalis Enterococcus faecium Epithelial Epithelial Cells Genetic study Germ-Free Host resistance Human Immune Immune signaling Individual Infection Inflammatory Inflammatory Bowel Diseases Integration Host Factors Intestines Laboratories Mammalian Cell Mediating Modeling Mus N-Acetylmuramoyl-L-alanine Amidase Pathogenesis Pathway interactions Peptidoglycan Prevention Probiotics Proteins Resistance Salmonella typhimurium Signal Pathway Signal Transduction Therapeutic Therapeutic Uses TimeLine commensal bacteria enteric infection enteric pathogen extracellular gut microbiota improved in vivo loss of function microbial microbiota mouse model novel pathogen pathogenic microbe prevent protective factors

项目摘要

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.

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。