title: A secreted bacterial peptidoglycan hydrolase enhances tolerance to enteric pathogens.
abstract: The intestinal microbiome modulates host susceptibility to enteric pathogens, but the specific protective factors and mechanisms of individual bacterial species are not fully characterized. We show that secreted antigen A (SagA) from Enterococcus faecium is sufficient to protect Caenorhabditis elegans against Salmonella pathogenesis by promoting pathogen tolerance. The NlpC/p60 peptidoglycan hydrolase activity of SagA is required and generates muramyl-peptide fragments that are sufficient to protect C. elegans against Salmonella pathogenesis in a tol-1-dependent manner. SagA can also be heterologously expressed and secreted to improve the protective activity of probiotics against Salmonella pathogenesis in C. elegans and mice. Our study highlights how protective intestinal bacteria can modify microbial-associated molecular patterns to enhance pathogen tolerance.
authors.affiliation: Laboratory of Chemical Biology and Microbial Pathogenesis, The Rockefeller University, New York, NY 10065, USA. krangan@rockefeller.edu hhang@rockefeller.edu.
authors.forename: Kavita J
authors.initials: KJ
authors.lastname: Rangan
authors.affiliation: Laboratory of Chemical Biology and Microbial Pathogenesis, The Rockefeller University, New York, NY 10065, USA. Laboratory of Mucosal Immunology, The Rockefeller University, New York, NY 10065, USA.
authors.forename: Virginia A
authors.initials: VA
authors.lastname: Pedicord
authors.affiliation: Laboratory of Chemical Biology and Microbial Pathogenesis, The Rockefeller University, New York, NY 10065, USA.
authors.forename: Yen-Chih
authors.initials: YC
authors.lastname: Wang
authors.affiliation: Laboratory of Chemical Biology and Microbial Pathogenesis, The Rockefeller University, New York, NY 10065, USA.
authors.forename: Byungchul
authors.initials: B
authors.lastname: Kim
authors.affiliation: Laboratory of Developmental Genetics, The Rockefeller University, New York, NY 10065, USA.
authors.forename: Yun
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Laboratory of Developmental Genetics, The Rockefeller University, New York, NY 10065, USA.
authors.forename: Shai
authors.initials: S
authors.lastname: Shaham
authors.affiliation: Laboratory of Mucosal Immunology, The Rockefeller University, New York, NY 10065, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Mucida
authors.affiliation: Laboratory of Chemical Biology and Microbial Pathogenesis, The Rockefeller University, New York, NY 10065, USA. krangan@rockefeller.edu hhang@rockefeller.edu.
authors.forename: Howard C
authors.initials: HC
authors.lastname: Hang
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology*; D001426:Bacterial Proteins / Q000276:immunology*; D017173:Caenorhabditis elegans / Q000276:immunology / Q000382:microbiology; D029742:Caenorhabditis elegans Proteins; D016984:Enterococcus faecium / Q000201:enzymology / Q000276:immunology*; D000069196:Gastrointestinal Microbiome / Q000276:immunology*; D054884:Host-Pathogen Interactions / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D009238:N-Acetylmuramoyl-L-alanine Amidase / Q000276:immunology*; D009419:Nerve Tissue Proteins; D019936:Probiotics; D012480:Salmonella Infections / Q000517:prevention & control*; D012486:Salmonella typhimurium / Q000276:immunology*
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D029742:Caenorhabditis elegans Proteins; D009419:Nerve Tissue Proteins; C439300:Tol-1 protein, C elegans; D009238:N-Acetylmuramoyl-L-alanine Amidase