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

Louise E. Tailford; C. David Owen; John Walshaw; Emmanuelle H. Crost; Jemma Hardy-Goddard; Gwenaelle Le Gall; Willem M. de Vos; Garry L. Taylor; Nathalie Juge

doi:10.1038/ncomms8624

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

Louise E. Tailford, C. David Owen, John Walshaw, Emmanuelle H. Crost, Jemma Hardy-Goddard, Gwenaelle Le Gall, Willem M. de Vos, Garry L. Taylor, Nathalie Juge^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Article number	7624
Number of pages	12
Journal	Nature Communications
Volume	6
DOIs	https://doi.org/10.1038/ncomms8624
Publication status	Published - 8 Jul 2015

Keywords

Inflammatory bowel-diseases
Sialic-acid
Streptococcus-pneumoniae
Entric pathogens
Crystal-structure
Mucus layers
Mucin
Bacteria
Specificity
Metabolism

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1038/ncomms8624Licence: CC BY

Owen_2015_NatComm_Discovery_CC
Copyright 2015 the Authors. This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
Final published version, 1.11 MBLicence: CC BY

Garry Lindsay Taylor
- glt2st-andrews.acuk
- School of Biology - Emeritus Professor
Person: Emeritus Professor

Cite this

@article{8ff6eeeca1e94b4ea597245aa7cb7a70,

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.",

keywords = "Inflammatory bowel-diseases, Sialic-acid, Streptococcus-pneumoniae, Entric pathogens, Crystal-structure, Mucus layers, Mucin, Bacteria, Specificity, Metabolism",

author = "Tailford, {Louise E.} and Owen, {C. David} and John Walshaw and Crost, {Emmanuelle H.} and Jemma Hardy-Goddard and {Le Gall}, Gwenaelle and {de Vos}, {Willem M.} and Taylor, {Garry L.} and Nathalie Juge",

note = "The authors acknowledge the support of the Biotechnology and Biological Sciences Research Council (BBSRC), this research was partly funded by the BBSRC Institute Strategic Programme for The Gut Health and Food Safety (BB/J004529/1) and by the BB/L008602/1 BBSRC-responsive mode grant. We also acknowledge support from the EU FP7 TORNADO programme. The research of WMdV was supported by the Academy of Finland, European Research Council and the Netherlands Organization for Scientific Research. ",

year = "2015",

month = jul,

day = "8",

doi = "10.1038/ncomms8624",

language = "English",

volume = "6",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Nature publishing group",

}

TY - JOUR

T1 - Discovery of intramolecular trans-sialidases in human gut microbiota suggests novel mechanisms of mucosal adaptation

AU - Tailford, Louise E.

AU - Owen, C. David

AU - Walshaw, John

AU - Crost, Emmanuelle H.

AU - Hardy-Goddard, Jemma

AU - Le Gall, Gwenaelle

AU - de Vos, Willem M.

AU - Taylor, Garry L.

AU - Juge, Nathalie

N1 - The authors acknowledge the support of the Biotechnology and Biological Sciences Research Council (BBSRC), this research was partly funded by the BBSRC Institute Strategic Programme for The Gut Health and Food Safety (BB/J004529/1) and by the BB/L008602/1 BBSRC-responsive mode grant. We also acknowledge support from the EU FP7 TORNADO programme. The research of WMdV was supported by the Academy of Finland, European Research Council and the Netherlands Organization for Scientific Research.

PY - 2015/7/8

Y1 - 2015/7/8

N2 - 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.

AB - 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.

KW - Inflammatory bowel-diseases

KW - Sialic-acid

KW - Streptococcus-pneumoniae

KW - Entric pathogens

KW - Crystal-structure

KW - Mucus layers

KW - Mucin

KW - Bacteria

KW - Specificity

KW - Metabolism

U2 - 10.1038/ncomms8624

DO - 10.1038/ncomms8624

M3 - Article

SN - 2041-1723

VL - 6

JO - Nature Communications

JF - Nature Communications

M1 - 7624

ER -

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

Abstract

Keywords

UN SDGs

Access to Document

Fingerprint

Profiles

Garry Lindsay Taylor

Cite this