A secreted bacterial peptidoglycan hydrolase enhances tolerance to enteric pathogens | Zendy

Kavita J. Rangan | Zendy; Virginia A. Pedicord | Zendy; YenChih Wang | Zendy; Byung-Chul Kim | Zendy; Yun Lu | Zendy; Shai Shaham | Zendy; Daniel Mucida | Zendy; Howard C. Hang | Zendy

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A secreted bacterial peptidoglycan hydrolase enhances tolerance to enteric pathogens

Author(s) -

Kavita J. Rangan,

Virginia A. Pedicord,

YenChih Wang,

Byung-Chul Kim,

Yun Lu,

Shai Shaham,

Daniel Mucida,

Howard C. Hang

Publication year - 2016

Publication title -

science

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 12.556

H-Index - 1186

eISSN - 1095-9203

pISSN - 0036-8075

DOI - 10.1126/science.aaf3552

Subject(s) - microbiology and biotechnology , peptidoglycan , salmonella , biology , pathogen , pathogenesis , caenorhabditis elegans , bacteria , enterococcus faecium , antibiotics , immunology , biochemistry , gene , genetics

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.

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