Enterococcus faecium secreted antigen A generates muropeptides to enhance host immunity and limit bacterial pathogenesis
Open accessAbstract
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.
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Strong signals are observed in the supernatant fractions of E. faecium, E. durans, E. hirae, and E. mundtii but not E. faecalis or E. gallinarum using antiserum against E. faecium SagA.
“Using antiserum raised against E. faecium SagA (19), strong signals were observed in the supernatant fractions of E. faecium, E. durans, E. hirae, and E. mundtii but not E. faecalis or E. gallinarum (Figs. 2D and S2C)”
From <i>Enterococcus</i> peptidoglycan remodeling promotes checkpoint inhibitor cancer immunotherapy (2021) · cites this paper as [19]
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References 69 · Cited by 120
- Authors
- Kim, B., Wang, Y.-C., Hespen, C. W., Espinosa, J., Salje, J., Rangan, K. J., Oren, D. A., Kang, J. Y., Pedicord, V. A., & Hang, H. C.
- Affiliations
- Laboratory of Chemical Biology and Microbial Pathogenesis, The Rockefeller University, New York, United States
- Rockefeller University (US)
- University of Oxford (GB)
- University of Cambridge (GB)
- Corresponding author
- Hang, Howard C
- ORCID
- Venue
- eLife
- Publisher
- eLife Sciences Publications, Ltd
- Published
- 2019-04-10
- Volume
- 8
- ISSN
- 2050-084X (ISSN-L)
- PMC
- PMC6483599
- OpenAlex
- W2937340088
- Cited by
- 120
- References
- 69
- Citations by year
- 2026: 10 · 2025: 18 · 2024: 28 · 2023: 28 · 2022: 12 · 2021: 10 · 2020: 9 · 2019: 4
- FWCI
- 3.50
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- eLife (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Apollo (University of Cambridge) (submittedVersion, cc-by)
- Apollo (cc-by)
- Funders
- Leona M. and Harry B. Helmsley Charitable Trust (Postdoctoral fellowship)
- National Center for Complementary and Integrative Health (F32AT010087)
- National Institute of General Medical Sciences (R01GM103593)
- Cancer Research Institute (Postdoctoral fellowship)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
- Keywords
- Enterococcus faecium, sagas, peptidoglycan hydrolase, muropeptides, peptidoglycan remodeling, intestinal barrier function, probiotics, Clostridium difficile, host immunity, commensal bacteria, pathogen tolerance
- MeSH terms
- Antigens, Bacterial, Humans, N-Acetylmuramoyl-L-alanine Amidase, Peptidoglycan, Protein Conformation, Enterococcus faecium, Crystallography, X-Ray, Nod2 Signaling Adaptor Protein, HEK293 Cells
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