title: Fut2-null mice display an altered glycosylation profile and impaired BabA-mediated Helicobacter pylori adhesion to gastric mucosa.
abstract: 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 Le(b) 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 Fucalpha(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.
authors.affiliation: Institute of Molecular Pathology and Immunology, University of Porto, Porto, Portugal.
authors.forename: Ana
authors.initials: A
authors.lastname: Magalhães
authors.forename: Joana
authors.initials: J
authors.lastname: Gomes
authors.forename: Mohd Nazri
authors.initials: MN
authors.lastname: Ismail
authors.forename: Stuart M
authors.initials: SM
authors.lastname: Haslam
authors.forename: Nuno
authors.initials: N
authors.lastname: Mendes
authors.forename: Hugo
authors.initials: H
authors.lastname: Osório
authors.forename: Leonor
authors.initials: L
authors.lastname: David
authors.forename: Jacques
authors.initials: J
authors.lastname: Le Pendu
authors.forename: Rainer
authors.initials: R
authors.lastname: Haas
authors.forename: Anne
authors.initials: A
authors.lastname: Dell
authors.forename: Thomas
authors.initials: T
authors.lastname: Borén
authors.forename: Celso A
authors.initials: CA
authors.lastname: Reis
mesh_terms: D018829:Adhesins, Bacterial / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D001422:Bacterial Adhesion / Q000235:genetics; D002139:Caliciviridae / Q000378:metabolism; D050260:Carbohydrate Metabolism / Q000235:genetics; D002240:Carbohydrate Sequence; D005647:Fucosyltransferases / Q000235:genetics*; D005753:Gastric Mucosa / Q000737:chemistry / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D054794:Glycomics; D006031:Glycosylation; D016481:Helicobacter Infections / Q000235:genetics / Q000473:pathology; D016480:Helicobacter pylori / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011134:Polysaccharides / Q000032:analysis / Q000302:isolation & purification; D000097631:Galactoside 2-alpha-L-fucosyltransferase
chemical_list: D018829:Adhesins, Bacterial; D005647:Fucosyltransferases; D011134:Polysaccharides; D000097631:Galactoside 2-alpha-L-fucosyltransferase; C400429:BabA protein, Helicobacter pylori; C500808:SabA protein, Helicobacter pylori
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