Affiliation:
1. Department of Immunology and Microbiology, Scripps Research
2. Department of Integrative Structural & Computational Biology, Scripps Research
3. Department of Chemistry, Scripps Research
Abstract
Enterococcus faecium
is a microbiota species in humans that can modulate host immunity
1
, but has also acquired antibiotic resistance and is a major cause of hospital-associated infections
2
. Notably, diverse strains of
E. faecium
produce SagA, a highly conserved peptidoglycan hydrolase that is sufficient to promote intestinal immunity
3–5
and immune checkpoint inhibitor antitumor activity
6
. However, the functions of SagA in
E. faecium
were unknown. Here we report that deletion of
sagA
impaired
E. faecium
growth and resulted in bulged and clustered enterococci due to defective peptidoglycan cleavage and cell separation. Moreover, Δ
sagA
showed increased antibiotic sensitivity, yielded lower levels of active muropeptides, displayed reduced activation of the peptidoglycan pattern-recognition receptor NOD2, and failed to promote cancer immunotherapy. Importantly, plasmid-based expression of SagA, but not its catalytically-inactive mutant, restored Δ
sagA
growth, production of active muropeptides and NOD2 activation. SagA is therefore essential for
E. faecium
growth, stress resistance and activation of host immunity.
Publisher
eLife Sciences Publications, Ltd