title: Discovery of intramolecular trans-sialidases in human gut microbiota suggests novel mechanisms of mucosal adaptation.
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.
authors.affiliation: The Gut Health and Food Safety Institute Strategic Programme, Institute of Food Research, Norwich Research Park, Norwich NR4 7UA, UK.
authors.forename: Louise E
authors.initials: LE
authors.lastname: Tailford
authors.affiliation: Biomolecular Sciences Building, University of St Andrews, St Andrews KY16 9ST, UK.
authors.forename: C David
authors.initials: CD
authors.lastname: Owen
authors.affiliation: 1] The Gut Health and Food Safety Institute Strategic Programme, Institute of Food Research, Norwich Research Park, Norwich NR4 7UA, UK [2] School of Computing Sciences, University of East Anglia, Norwich NR4 7TJ, UK.
authors.forename: John
authors.initials: J
authors.lastname: Walshaw
authors.affiliation: The Gut Health and Food Safety Institute Strategic Programme, Institute of Food Research, Norwich Research Park, Norwich NR4 7UA, UK.
authors.forename: Emmanuelle H
authors.initials: EH
authors.lastname: Crost
authors.affiliation: The Gut Health and Food Safety Institute Strategic Programme, Institute of Food Research, Norwich Research Park, Norwich NR4 7UA, UK.
authors.forename: Jemma
authors.initials: J
authors.lastname: Hardy-Goddard
authors.affiliation: The Gut Health and Food Safety Institute Strategic Programme, Institute of Food Research, Norwich Research Park, Norwich NR4 7UA, UK.
authors.forename: Gwenaelle
authors.initials: G
authors.lastname: Le Gall
authors.affiliation: 1] Laboratory of Microbiology, Wageningen UR, Building 316, Dreijenplein 10, 6703 HB Wageningen, The Netherlands [2] Departments of Bacteriology and Immunology and Veterinary Bioscience, University of Helsinki, PO Box 66, FI-00014 Helsinki, Finland.
authors.forename: Willem M
authors.initials: WM
authors.lastname: de Vos
authors.affiliation: Biomolecular Sciences Building, University of St Andrews, St Andrews KY16 9ST, UK.
authors.forename: Garry L
authors.initials: GL
authors.lastname: Taylor
authors.affiliation: The Gut Health and Food Safety Institute Strategic Programme, Institute of Food Research, Norwich Research Park, Norwich NR4 7UA, UK.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Juge
mesh_terms: D000222:Adaptation, Physiological / Q000502:physiology*; D015964:Gene Expression Regulation, Bacterial / Q000502:physiology*; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007413:Intestinal Mucosa / Q000382:microbiology*; D009077:Mucins / Q000378:metabolism; D009439:Neuraminidase / Q000235:genetics / Q000378:metabolism*; D045857:Ruminococcus / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism
chemical_list: D006023:Glycoproteins; D009077:Mucins; C069715:trans-sialidase; D009439:Neuraminidase