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

Published version
Peer-reviewed

Type

Article

Change log

Authors

Wang, Yen-Chih 
Salje, Jeanne 

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.

Description

Keywords

Enterococcus, NOD2, biochemistry, chemical biology, commensal bacteria, intestinal barrier, microbiota, peptidoglycan, Antigens, Bacterial, Crystallography, X-Ray, Enterococcus faecium, HEK293 Cells, Humans, N-Acetylmuramoyl-L-alanine Amidase, Nod2 Signaling Adaptor Protein, Peptidoglycan, Protein Conformation

Journal Title

Elife

Conference Name

Journal ISSN

2050-084X
2050-084X

Volume Title

8

Publisher

eLife Sciences Publications, Ltd