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Enterococcus faecium secreted antigen A generates muropeptides to enhance host immunity and limit bacterial pathogenesis

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...

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Autores principales: Kim, Byungchul, Wang, Yen-Chih, Hespen, Charles W, Espinosa, Juliel, Salje, Jeanne, Rangan, Kavita J, Oren, Deena A, Kang, Jin Young, Pedicord, Virginia A, Hang, Howard C
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6483599/
https://www.ncbi.nlm.nih.gov/pubmed/30969170
http://dx.doi.org/10.7554/eLife.45343
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author Kim, Byungchul
Wang, Yen-Chih
Hespen, Charles W
Espinosa, Juliel
Salje, Jeanne
Rangan, Kavita J
Oren, Deena A
Kang, Jin Young
Pedicord, Virginia A
Hang, Howard C
author_facet Kim, Byungchul
Wang, Yen-Chih
Hespen, Charles W
Espinosa, Juliel
Salje, Jeanne
Rangan, Kavita J
Oren, Deena A
Kang, Jin Young
Pedicord, Virginia A
Hang, Howard C
author_sort Kim, Byungchul
collection PubMed
description 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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spelling pubmed-64835992019-04-29 Enterococcus faecium secreted antigen A generates muropeptides to enhance host immunity and limit bacterial pathogenesis Kim, Byungchul Wang, Yen-Chih Hespen, Charles W Espinosa, Juliel Salje, Jeanne Rangan, Kavita J Oren, Deena A Kang, Jin Young Pedicord, Virginia A Hang, Howard C eLife Biochemistry and Chemical Biology 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. eLife Sciences Publications, Ltd 2019-04-10 /pmc/articles/PMC6483599/ /pubmed/30969170 http://dx.doi.org/10.7554/eLife.45343 Text en © 2019, Kim et al http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Biochemistry and Chemical Biology
Kim, Byungchul
Wang, Yen-Chih
Hespen, Charles W
Espinosa, Juliel
Salje, Jeanne
Rangan, Kavita J
Oren, Deena A
Kang, Jin Young
Pedicord, Virginia A
Hang, Howard C
Enterococcus faecium secreted antigen A generates muropeptides to enhance host immunity and limit bacterial pathogenesis
title Enterococcus faecium secreted antigen A generates muropeptides to enhance host immunity and limit bacterial pathogenesis
title_full Enterococcus faecium secreted antigen A generates muropeptides to enhance host immunity and limit bacterial pathogenesis
title_fullStr Enterococcus faecium secreted antigen A generates muropeptides to enhance host immunity and limit bacterial pathogenesis
title_full_unstemmed Enterococcus faecium secreted antigen A generates muropeptides to enhance host immunity and limit bacterial pathogenesis
title_short Enterococcus faecium secreted antigen A generates muropeptides to enhance host immunity and limit bacterial pathogenesis
title_sort enterococcus faecium secreted antigen a generates muropeptides to enhance host immunity and limit bacterial pathogenesis
topic Biochemistry and Chemical Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6483599/
https://www.ncbi.nlm.nih.gov/pubmed/30969170
http://dx.doi.org/10.7554/eLife.45343
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