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

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.

journal_name

Elife

journal_title

eLife

authors

Kim B,Wang YC,Hespen CW,Espinosa J,Salje J,Rangan KJ,Oren DA,Kang JY,Pedicord VA,Hang HC

doi

10.7554/eLife.45343

subject

Has Abstract

pub_date

2019-04-10 00:00:00

issn

2050-084X

pii

45343

journal_volume

8

pub_type

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