Discovery of intramolecular trans-sialidases in human gut microbiota suggests novel mechanisms of mucosal adaptation

Nat Commun. 2015 Jul 8;6:7624. doi: 10.1038/ncomms8624.

Abstract

The gastrointestinal mucus layer is colonized by a dense community of microbes catabolizing dietary and host carbohydrates during their expansion in the gut. Alterations in mucosal carbohydrate availability impact on the composition of microbial species. Ruminococcus gnavus is a commensal anaerobe present in the gastrointestinal tract of >90% of humans and overrepresented in inflammatory bowel diseases (IBD). Using a combination of genomics, enzymology and crystallography, we show that the mucin-degrader R. gnavus ATCC 29149 strain produces an intramolecular trans-sialidase (IT-sialidase) that cleaves off terminal α2-3-linked sialic acid from glycoproteins, releasing 2,7-anhydro-Neu5Ac instead of sialic acid. Evidence of IT-sialidases in human metagenomes indicates that this enzyme occurs in healthy subjects but is more prevalent in IBD metagenomes. Our results uncover a previously unrecognized enzymatic activity in the gut microbiota, which may contribute to the adaptation of intestinal bacteria to the mucosal environment in health and disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptation, Physiological / physiology*
  • Gene Expression Regulation, Bacterial / physiology*
  • Gene Expression Regulation, Enzymologic / physiology
  • Glycoproteins / genetics
  • Glycoproteins / metabolism*
  • Humans
  • Intestinal Mucosa / microbiology*
  • Mucins / metabolism
  • Neuraminidase / genetics
  • Neuraminidase / metabolism*
  • Ruminococcus / enzymology*
  • Ruminococcus / genetics
  • Ruminococcus / metabolism

Substances

  • Glycoproteins
  • Mucins
  • trans-sialidase
  • Neuraminidase

Associated data

  • PDB/4X47
  • PDB/4X49
  • PDB/4X4A
  • PDB/4X6K