Muc5ac gastric mucin glycosylation is shaped by FUT2 activity and functionally impacts Helicobacter pylori binding

envie a um amigo share this

Muc5ac gastric mucin glycosylation is shaped by FUT2 activity and functionally impacts Helicobacter pylori binding

Quinta, 18.08.2016

Authors and Affiliations:

Ana Magalhães1,2, Yannick Rossez3, Catherine Robbe-Masselot3, Emmanuel Maes3, Joana Gomes1,2, Anna Shevtsova4, Jeanna Bugaytsova4, Thomas Borén4 & Celso A. Reis1,2,5,6

1 i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Rua Júlio Amaral de Carvalho, 45, 4200- 135 Porto, Portugal.

2 Institute of Molecular Pathology and Immunology of University of Porto, Ipatimup, Rua Júlio Amaral de Carvalho, 45, 4200-135 Porto, Portugal.

3 Structural and Functional Glycobiology Unit, UMR CNRS 8576, University of Lille, 59655 Villeneuve d’Ascq, France.

4 Department of Medical Biochemistry and Biophysics, Umeå University, SE-901 87 Umeå, Sweden.

5 Medical Faculty, University of Porto, Al. Prof. Hernâni Monteiro, 4200–319

Porto, Portugal.

6 Instituto de Ciências Biomédicas de Abel Salazar (ICBAS), University of Porto, Rua de Jorge Viterbo Ferreira no 228, 4050-313 Porto, Portugal.

 

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 α1,2-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.

 

Journal: Scientific Reports

 

Link: http://www.nature.com/articles/srep25575