Enterococcus faecium secreted antigen A generates muropeptides to enhance host immunity and limit bacterial pathogenesis
- The Rockefeller University, United States
- University of Oxford, United Kingdom
Abstract
We discovered that Enterococcus faecium (E. faecium), a ubiquitous commensal bacterium, and its secreted peptidoglycan hydrolase (SagA) were sufficient to enhance intestinal barrier function and pathogen tolerance, but the precise biochemical mechanism was unknown. Here we show E. faecium has unique peptidoglycan composition and remodeling activity through SagA, which generates smaller muropeptides that more effectively activates nucleotide-binding oligomerization domain-containing protein 2 (NOD2) in mammalian cells. Our structural and biochemical studies show that SagA is a NlpC/p60-endopeptidase that preferentially hydrolyzes crosslinked Lys-type peptidoglycan fragments. SagA secretion and NlpC/p60-endopeptidase activity was required for enhancing probiotic bacteria activity against Clostridium difficile pathogenesis in vivo. Our results demonstrate that the peptidoglycan composition and hydrolase activity of specific microbiota species can activate host immune pathways and enhance tolerance to pathogens.
Data availability
All data generated or analyzed during this study are included in the manuscript and supporting files.Diffraction data have been deposited in PDB under the accession code 6B8C.
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Crystal structure of NlpC/p60 domain of peptidoglycan hydrolase SagARCSB Protein Data Bank, 6B8C.
Article and author information
Author details
Funding
National Institute of General Medical Sciences (R01GM103593)
- Byungchul Kim
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Kim Orth, HHMI/University of Texas Southwestern Medical Center, United States
Version history
- Received: January 18, 2019
- Accepted: April 4, 2019
- Accepted Manuscript published: April 10, 2019 (version 1)
- Version of Record published: April 25, 2019 (version 2)
Copyright
© 2019, Kim et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Enterococcus faecium secreted antigen A generates muropeptides to enhance host immunity and limit bacterial pathogenesis
eLife 8:e45343.
https://doi.org/10.7554/eLife.45343
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