HOST TOLERANCE: A secreted bacterial peptidoglycan hydrolase enhances tolerance to enteric pathogens

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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) fromEnterococcus faeciumis sufficient to protectCaenorhabditis elegansagainstSalmonellapathogenesis by promoting pathogen tolerance. The NlpC/p60 peptidoglycan hydrolase activity of SagA is required and generates muramylpeptide fragments that are sufficient to protectC. elegansagainstSalmonellapathogenesis in atol-1-dependent manner. SagA can also be heterologously expressed and secreted to improve the protective activity of probiotics againstSalmonellapathogenesis inC. elegansand mice. Our study highlights how protective intestinal bacteria can modify microbialassociated molecular patterns to enhance pathogen tolerance.

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