Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

We discovered that <i>Enterococcus faecium</i> (<i>E. faecium</i>), 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 <i>E. faecium</i> 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 <i>Clostridium difficile</i> pathogenesis <i>in vivo</i>. Our results demonstrate that the peptidoglycan composition and hydrolase activity of specific microbiota species can activate host immune pathways and enhance tolerance to pathogens.

Original publication

DOI

10.7554/elife.45343

Type

Journal article

Journal

eLife

Publication Date

10/04/2019

Volume

8

Addresses

Laboratory of Chemical Biology and Microbial Pathogenesis, The Rockefeller University, New York, United States.

Keywords

Humans, Enterococcus faecium, N-Acetylmuramoyl-L-alanine Amidase, Peptidoglycan, Antigens, Bacterial, Crystallography, X-Ray, Protein Conformation, Nod2 Signaling Adaptor Protein, HEK293 Cells