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.
Highlights
The thick mucus layer of the gut provides a barrier to infiltration of the underlying epithelia by both the normal microbiota and enteric pathogens
The genes and proteins highlighted in these studies included many putative exo-acting enzymes from CAZy families that have previously been identified as involved degradation of Oglycans, such as sialidases (GH33) and fucosidases (GH29 and GH95; Supplementary Figs. 1–3)
We describe the characterisation of members of the glycoside hydrolase 16 (GH16) family that have a specificity for the Galβ1,4GlcNAc linkage in the polyLacNAc chains found in mucins and other O-glycans
Summary
The thick mucus layer of the gut provides a barrier to infiltration of the underlying epithelia by both the normal microbiota and enteric pathogens. 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 likely involved in the initial step in mucin breakdown. The heterogeneity between individual O-glycan chains leads to a highly complex macromolecule and it is this complexity that provides some resistance to microbial degradation and contributes to the mucus layers’ protective role[4] Despite this heterogeneity, some prominent bacterial members of the microbiota have developed the capacity to graze on mucins, including certain Bacteroides spp. and Akkermanisa muciniphila[5,6,7,8,9]. We provide evidence these endo Oglycanases could be exploited as tools to explore the composition of human O-glycans from a range of different sources, with potential applications in both basic research and precision medicine
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