RT Journal Article
SR Electronic
T1 Prominent members of the human gut microbiota express endo-acting O-glycanases to initiate mucin breakdown
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 835843
DO 10.1101/835843
A1 Lucy I. Crouch
A1 Marcelo V. Liberato
A1 Paulina A. Urbanowicz
A1 Arnaud Baslé
A1 Christopher A. Lamb
A1 Christopher J. Stewart
A1 Katie Cooke
A1 Mary Doona
A1 Stephanie Needham
A1 Richard R. Brady
A1 Janet E. Berrington
A1 Katarina Madunic
A1 Manfred Wuhrer
A1 Peter Chater
A1 Jeffery P. Pearson
A1 Robert Glowacki
A1 Eric C. Martens
A1 Fuming Zhang
A1 Robert J. Linhardt
A1 Daniel I. R. Spencer
A1 David N. Bolam
YR 2019
UL http://biorxiv.org/content/early/2019/11/09/835843.abstract
AB The human gut microbiota (HGM) are closely associated with health, development and disease. The thick intestinal mucus layer, especially in the colon, is the key barrier between the contents of the lumen and the epithelial cells, providing protection against infiltration by the microbiota as well potential pathogens. The upper layer of the colonic mucus is a niche for a subset of the microbiota which utilise the mucin glycoproteins as a nutrient source and mucin grazing by the microbiota appears to play a key role in maintaining barrier function as well as community stability. Despite the importance of mucin breakdown for gut health, the mechanisms by which gut bacteria access this complex glycoprotein are not well understood. The current model for mucin degradation involves exclusively exo-acting glycosidases that sequentially trim monosaccharides from the termini of the glycan chains to eventually allow access to the mucin peptide backbone by proteases. However, this model is in direct contrast to the Sus paradigm of glycan breakdown used by the Bacteroidetes which involves extracellular cleavage of glycans by surface located endo-acting enzymes prior to import of the oligosaccharide products. Here we describe the discovery and characterisation of endo-acting family 16 glycoside hydrolases (GH16s) from prominent mucin degrading gut bacteria that specifically target the oligosaccharide side chains of intestinal mucins from both animals and humans. These endo-acting O-glycanases display β1,4-glactosidase activity and in several cases are surface located indicating they are involved in the initial step in mucin breakdown. The data suggest a new paradigm for mucin breakdown by the microbiota and the endo-mucinases provide a potential tool to explore changes that occur in mucin structure in intestinal disorders such as inflammatory bowel disease and colon cancer.