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Glycobiology Advance Access originally published online on August 25, 2009
Glycobiology 2009 19(12):1525-1536; doi:10.1093/glycob/cwp131
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© The Author 2009. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

Fut2-null mice display an altered glycosylation profile and impaired BabA-mediated Helicobacter pylori adhesion to gastric mucosa

Ana Magalhães2, Joana Gomes2, Mohd Nazri Ismail3, Stuart M Haslam3, Nuno Mendes2, Hugo Osório2, Leonor David2,4, Jacques Le Pendu5, Rainer Haas6, Anne Dell3, Thomas Borén7 and Celso A Reis1,2,4

2 Institute of Molecular Pathology and Immunology, University of Porto, Porto, Portugal
3 Division of Molecular Biosciences, Faculty of Natural Sciences, Imperial College London, London, UK
4 Medical Faculty, University of Porto, Porto, Portugal
5 INSERM, U892, University of Nantes, Nantes, France
6 Max von Pettenkofer Institute, LMU München, München, Germany
7 Department of Medical Biochemistry and Biophysics, Umeå University, Umeå, Sweden

1 To whom correspondence should be addressed: Tel: +351-225570700; Fax: +351-225570799; e-mail: celsor{at}ipatimup.pt

Received on July 2, 2009; revised on August 21, 2009; accepted on August 21, 2009

Glycoconjugates expressed on gastric mucosa play a crucial role in host–pathogen interactions. The FUT2 enzyme catalyzes the addition of terminal {alpha}(1,2)fucose residues, producing the H type 1 structure expressed on the surface of epithelial cells and in mucosal secretions of secretor individuals. Inactivating mutations in the human FUT2 gene are associated with reduced susceptibility to Helicobacter pylori infection. H. pylori infects over half the world's population and causes diverse gastric lesions, from gastritis to gastric cancer. H. pylori adhesion constitutes a crucial step in the establishment of a successful infection. The BabA adhesin binds the Leb and H type 1 structures expressed on gastric mucins, while SabA binds to sialylated carbohydrates mediating the adherence to inflamed gastric mucosa. In this study, we have used an animal model of nonsecretors, Fut2-null mice, to characterize the glycosylation profile and evaluate the effect of the observed glycan expression modifications in the process of H. pylori adhesion. We have demonstrated expression of terminal difucosylated glycan structures in C57Bl/6 mice gastric mucosa and that Fut2-null mice showed marked alteration in gastric mucosa glycosylation, characterized by diminished expression of {alpha}(1,2)fucosylated structures as indicated by lectin and antibody staining and further confirmed by mass spectrometry analysis. This altered glycosylation profile was further confirmed by the absence of Fuc{alpha}(1,2)-dependent binding of calicivirus virus-like particles. Finally, using a panel of H. pylori strains, with different adhesin expression profiles, we have demonstated an impairment of BabA-dependent adhesion of H. pylori to Fut2-null mice gastric mucosa, whereas SabA-mediated binding was not affected.

Key words: {alpha}1 / 2fucosyltransferase / BabA / bacterial adhesion / Helicobacter pylori / Lewis antigens


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