Elucidation of Commensal Bacteria Mechanisms Required for Host Protection

阐明宿主保护所需的共生细菌机制

• 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
• 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

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.

项目总结

项目成果

A secreted bacterial peptidoglycan hydrolase enhances tolerance to enteric pathogens.

• DOI: 10.1126/science.aaf3552
• 发表时间: 2016-09-23
• 期刊: Science (New York, N.Y.)
• 作者: Rangan KJ;Pedicord VA;Wang YC;Kim B;Lu Y;Shaham S;Mucida D;Hang HC
• 通讯作者: Hang HC

Anti-infective bile acids bind and inactivate a Salmonella virulence regulator.

• DOI: 10.1038/s41589-022-01122-3
• 发表时间: 2023-01
• 期刊: NATURE CHEMICAL BIOLOGY
• 影响因子: 14.8
• 作者: Yang, Xinglin;Stein, Kathryn R.;Hang, Howard C.
• 通讯作者: Hang, Howard C.

Peptidoglycan Metabolite Photoaffinity Reporters Reveal Direct Binding to Intracellular Pattern Recognition Receptors and Arf GTPases.

• DOI: 10.1021/acschembio.8b01038
• 发表时间: 2019-02
• 期刊: ACS chemical biology
• 影响因子: 4
• 作者: Yen-Chih Wang;Nathan P. Westcott;Matthew E. Griffin;H. Hang