A secreted bacterial peptidoglycan hydrolase enhances tolerance to enteric pathogens.

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PubMed ID: 27708039

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Rangan KJ, Pedicord VA, Wang YC, Kim B, Lu Y, Shaham S, Mucida D, Hang HC

Science. Sep 2016

COMMENT: Association of dysbiosis with different disease has been described years ago. However, it has been more difficult to find individual bacterial species and factors involved in host protection. It has been described that Enterococci can attenuate host susceptibility to enteric pathogens, like Salmonella and, thus, nonpathogenic Enterococcus faecium has been used as probiotic. 

The authors took C. elegans as a model to analyze why E. faecium has a beneficial effect. The experiments showed that after S. typhimurium infection C. elegans survival was increased in animals fed with E. faecium before infection as compared with animals fed with Escherichia coli OP50 or Bacillus subtilis 168 and they were also more resistant to the pathogenic effects of E. coli OP50 and Enterococcus faecalis V583. Thus, the mechanisms involved in protection seem to be active against diverse enteric pathogens. The experiments suggested and that E. faecium does not prevent S. typhimurium colonization or replication but may enhance host tolerance to pathogens, probably by means of improving epithelial barrier integrity.

E. faecium culture supernatant was as effective as live bacterial cultures in inhibiting S. typhimurium pathogenic effects. The activity of the supernatant was abolished by proteinase K and the secreted antigen SagA was the most abundant protein identified in the supernatant.

C. elegans encodes one homolog of Toll-like receptors (TLR), tol-1 . SagA-mediated protection was not seen in tol-1 mutants which suggests that SagA enhances pathogen tolerance through tol-1 signaling .

SagA is a functional hydrolase that can cleave peptidoglycan and the authors showed that SagA-generated peptidoglycan fragments, and not SagA itself, are responsible for enhancing pathogen tolerance. SagA-generated peptidoglycan fragments, MurNAc and MurNAc-L-Ala, was sufficient to inhibit S. typhimurium pathogenesis.


Eduardo Pareja