Please use this identifier to cite or link to this item:
https://hdl.handle.net/10216/119046
Author(s): | Magalhães, A Rossez, Y Robbe-Masselot, C Maes, E Gomes, J Shevtsova, A Bugaytsova, J Borén, T Reis, CA |
Title: | Muc5ac gastric mucin glycosylation is shaped by FUT2 activity and functionally impacts Helicobacter pylori binding |
Publisher: | Nature Publishing Group |
Issue Date: | 2016 |
Abstract: | The gastrointestinal tract is lined by a thick and complex layer of mucus that protects the mucosal epithelium from biochemical and mechanical aggressions. This mucus barrier confers protection against pathogens but also serves as a binding site that supports a sheltered niche of microbial adherence. The carcinogenic bacteria Helicobacter pylori colonize the stomach through binding to host glycans present in the glycocalyx of epithelial cells and extracellular mucus. The secreted MUC5AC mucin is the main component of the gastric mucus layer, and BabA-mediated binding of H. pylori to MUC5AC confers increased risk for overt disease. In this study we unraveled the O-glycosylation profile of Muc5ac from glycoengineered mice models lacking the FUT2 enzyme and therefore mimicking a non-secretor human phenotype. Our results demonstrated that the FUT2 determines the O-glycosylation pattern of Muc5ac, with Fut2 knock-out leading to a marked decrease in a1,2-fucosylated structures and increased expression of the terminal type 1 glycan structure Lewis-a. Importantly, for the first time, we structurally validated the expression of Lewis-a in murine gastric mucosa. Finally, we demonstrated that loss of mucin FUT2-mediated fucosylation impairs gastric mucosal binding of H. pylori BabA adhesin, which is a recognized feature of pathogenicity. |
Subject: | Adhesins, Bacterial/metabolism Animals Bacterial Adhesion Fucosyltransferases/genetics Fucosyltransferases/metabolism Gastric Mucins/metabolism Gastric Mucosa/metabolism Glycosylation Helicobacter Infections/metabolism Helicobacter Infections/microbiology Helicobacter pylori/metabolism Helicobacter pylori/physiology Humans Lewis Blood-Group System/metabolism Mice, Inbred C57BL Mice, Knockout Mucin 5AC/metabolism Mucus/metabolism Polysaccharides/metabolism Protein Binding |
URI: | https://hdl.handle.net/10216/119046 |
Source: | Scientific Reports, vol.6:25575 |
Related Information: | info:eu-repo/grantAgreement/FCT/COMPETE/133784/PT info:eu-repo/grantAgreement/FCT/COMPETE/125428/PT info:eu-repo/grantAgreement/FCT/SFRH/SFRH%2FBPD%2F75871%2F2011/PT |
Document Type: | Artigo em Revista Científica Internacional |
Rights: | openAccess |
License: | https://creativecommons.org/licenses/by/4.0/ |
Appears in Collections: | I3S - Artigo em Revista Científica Internacional |
Files in This Item:
File | Description | Size | Format | |
---|---|---|---|---|
Magalhaes Scientific Rep 2016.pdf | 1.9 MB | Adobe PDF | View/Open |
This item is licensed under a Creative Commons License