Prominent members of the human gut microbiota express endo-acting O-glycanases to initiate mucin breakdown

Lucy I. Crouch (), Marcelo V. Liberato, Paulina A. Urbanowicz, Arnaud Baslé, Christopher A. Lamb, Christopher J. Stewart, Katie Cooke, Mary Doona, Stephanie Needham, Richard R. Brady, Janet E. Berrington, Katarina Madunic, Manfred Wuhrer, Peter Chater, Jeffery P. Pearson, Robert Glowacki, Eric C. Martens, Fuming Zhang, Robert J. Linhardt, Daniel I. R. Spencer and David N. Bolam ()
Additional contact information
Lucy I. Crouch: Newcastle University
Marcelo V. Liberato: Universidade de Sorocaba, Programa de Processos Tecnológicos e Ambientais
Paulina A. Urbanowicz: Ludger Ltd, Culham Science Centre
Arnaud Baslé: Newcastle University
Christopher A. Lamb: Newcastle upon Tyne Hospitals NHS Foundation Trust
Christopher J. Stewart: Newcastle University
Katie Cooke: Newcastle University
Mary Doona: Newcastle upon Tyne Hospitals NHS Foundation Trust
Stephanie Needham: Newcastle upon Tyne Hospitals NHS Foundation Trust
Richard R. Brady: Newcastle upon Tyne Hospitals NHS Foundation Trust
Janet E. Berrington: Royal Victoria Infirmary
Katarina Madunic: Leiden University Medical Centre
Manfred Wuhrer: Leiden University Medical Centre
Peter Chater: Newcastle University
Jeffery P. Pearson: Newcastle University
Robert Glowacki: University of Michigan Medical School
Eric C. Martens: University of Michigan Medical School
Fuming Zhang: Rensselaer Polytechnic Institute
Robert J. Linhardt: Rensselaer Polytechnic Institute
Daniel I. R. Spencer: Ludger Ltd, Culham Science Centre
David N. Bolam: Newcastle University

Nature Communications, 2020, vol. 11, issue 1, 1-13

Abstract: Abstract The thick mucus layer of the gut provides a barrier to infiltration of the underlying epithelia by both the normal microbiota and enteric pathogens. Some members of the microbiota utilise mucin glycoproteins as a nutrient source, but a detailed understanding of the mechanisms used to breakdown these complex macromolecules is lacking. Here we describe the discovery and characterisation of endo-acting enzymes from prominent mucin-degrading bacteria that target the polyLacNAc structures within oligosaccharide side chains of both animal and human mucins. These O-glycanases are part of the large and diverse glycoside hydrolase 16 (GH16) family and are often lipoproteins, indicating that they are surface located and thus likely involved in the initial step in mucin breakdown. These data provide a significant advance in our knowledge of the mechanism of mucin breakdown by the normal microbiota. Furthermore, we also demonstrate the potential use of these enzymes as tools to explore changes in O-glycan structure in a number of intestinal disease states.

Date: 2020
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DOI: 10.1038/s41467-020-17847-5

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