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Infection by Helicobacter pylori expressing the BabA adhesin is influenced by the secretor phenotype
Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
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2008 (English)In: Journal of Pathology, ISSN 0022-3417, E-ISSN 1096-9896, Vol. 215, no 3, 308-316 p.Article in journal (Refereed) Published
Abstract [en]

Helicobacter pylori (Hp) infects half the world's population and causes diverse gastric lesions, from gastritis to gastric cancer. Our aim was to evaluate the significance of secretor and Lewis status in infection and in vitro adherence by Hp expressing BabA adhesin. We enrolled 304 Hp-infected individuals from Northern Portugal. Gastric biopsies, blood and saliva were collected. Polymerase chain reaction (PCR) and immunofluorescence were used to detect BabA+ Hp in gastric biopsies. In vitro adherence by a BabA expressing Hp strain to gastric biopsies was performed. Secretor status was identified by Ulex, a lectin that recognizes secretor-dependent glycan structures in saliva and in gastric mucosa, and by Lewis(a/b) antibodies, and indirectly by identification of an inactivating mutation in the FUT2 gene (G428A). BabA status of infecting Hp was associated with CagA and VacAs1 (p < 0.05), intercellular localization of Hp (p < 0.01) and the presence of intestinal metaplasia (p < 0.05) and degenerative alterations (p < 0.005) in the biopsies. BabA was associated (p < 0.05) with Ulex staining of gastric biopsies and, although not significantly, to absence of homozygosity for FUT2 G428A inactivating polymorphism. In vitro Hp adherence was higher in cases wild-type or heterozygous for FUT2 G428A mutation (p < 0.0001), cases staining for Ulex (p < 0.0001) and a(-)b+ and a(-)b(-) secretor phenotypes (p < 0.001). In conclusion, BabA+ Hp infection/adhesion is secretor-dependent and associated with the severity of gastric lesions.

Place, publisher, year, edition, pages
2008. Vol. 215, no 3, 308-316 p.
Keyword [en]
Helicobacter pylori; blood-group antigen binding adhesin (BabA); Lewis antigens; secretor status; gastritis; intestinal metaplasia; stomach; immunofluorescence
National Category
Microbiology in the medical area
URN: urn:nbn:se:umu:diva-22412DOI: 10.1002/path.2363PubMedID: 18498114OAI: diva2:216299
Available from: 2009-05-07 Created: 2009-05-07 Last updated: 2012-10-26Bibliographically approved
In thesis
1. Helicobacter pylori: multitalented adaptation of binding properties
Open this publication in new window or tab >>Helicobacter pylori: multitalented adaptation of binding properties
2012 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Helicobacter pylori infects and persistently colonizes the stomach, which results in gastritis and in some individuals peptic ulcer disease or gastric cancer. Adherence of H. pylori to the epithelium is an important factor for development of disease. Attachment is mediated by the adhesins BabA and SabA that binds the ABO/Leb blood group antigens and sialylated glycoconjugates respectively.  High-affinity attachment could be anticipated to be of disadvantage for H. pylori because epithelial cells have a fast turnover rate and the dislocated and shed epithelial cells would carry attached bacteria to the acidic gastric juice in the lumen. However, here we describe that H. pylori manage to adapt to this innate clearance mechanism by unique acid regulatory binding properties of its adhesins. We propose that pH regulated binding properties enable bacteria to detachment from host cells for chemotactic guided motility and successful return to the more neutral epithelium for a fresh restart of the infectious cycle. By comparison of BabA from different stomach loci we identified amino acid key position for acid regulated binding activity.

Previous studies found lower prevalence of Leb-binding among H. pylori isolates from southern Europe compared to Sweden. Here we tested if the reduced prevalence of Leb-binding could be explained by a novel binding mode; in among Spanish strains, we identified S812 that demonstrates preference for multivalent binding to ABO antigens in glycolipids; we found that 812 BabA had drifted in its preferred binding epitope away from the consensus a1,2fucosylation and towards the blood group A and B derivatives. Such epitope drift might in particular optimize binding to ABO antigens in densely packed lipid rafts.

In parallel, we studied the influence of BabA for disease progression by an inventory of gastric biopsies. BabA correlated both with the oncoprotein CagA, the VacAs1 toxin and, in addition, to severe disease progression. We further correlate BabA expression with positive secretor phenotype and stronger adhesion of H. pylori in vitro.

For functional adherence studies in vitro, we constructed a recombinant Leb-expressing cell lineage that supports BabA mediated H. pylori attachment.

Place, publisher, year, edition, pages
Umeå: Umeå university, 2012. 52 p.
Umeå University medical dissertations, ISSN 0346-6612 ; 1524
Helicobacter pylori, adherence, receptor specificity, adaptation, pH, BabA, Leb, recombination, secretor phenotype, recombinant cell lines
National Category
Microbiology in the medical area
urn:nbn:se:umu:diva-60751 (URN)978-91-7459-487-4 (ISBN)
Public defence
2012-11-16, KB3A9, KBC-huset, Umeå, 09:00 (English)
Available from: 2012-10-26 Created: 2012-10-25 Last updated: 2012-10-26Bibliographically approved

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