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Studies of Lewis antigens and H. pylori adhesion in CHO cell lines engineered to express Lewis b determinants
Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.ORCID-id: 0000-0003-1615-0583
Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
Vise andre og tillknytning
2008 (engelsk)Inngår i: Glycobiology, ISSN 0959-6658, E-ISSN 1460-2423, Vol. 18, nr 7, s. 494-501Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

Many microbes bind and adhere via adhesins to host cell carbohydrates as an initial step for infection. Therefore, cell lines expressing Lewis b (Le(b)) determinants were generated as a potential model system for Helicobacter pylori colonization and infection, and their expression of blood group Lewis determinants was characterized. CHO-K1 cells were stably transfected with selected glycosyltransferase cDNAs, and two Le(b) positive clones, 1C5 and 2C2, were identified. Expression of Lewis (Le(a), Le(b), Le(x), and Le(y)) determinants was analyzed by flow cytometry of intact cells, SDS-PAGE/Western blot of solubilized glycoproteins, and thin layer chromatography immunostaining of isolated glycolipids (GL). Binding of H. pylori to cells was examined by microscopy and quantified. Flow cytometry showed that 1C5 and 2C2 were Le(a) and Le(b) positive. 1C5 expressed Le(b) on O-linked, but not N-linked, glycans and only weakly on GLs. In contrast, 2C2 expressed Le(b) on N-, O-glycans, and GLs. Furthermore, both clones expressed Le(a) on N- and O-glycans but not on GLs. 2C2, but not 1C5, stained positively for Le(y) on N-linked glycans and GLs. Both clones, as well as the parental CHO-K1 cells, expressed Le(x) on GLs. A Le(b)-binding H. pylori strain bound to the 1C5 and 2C2 cells. In summary, two glycosyltransferase transfected CHO-K1 cell clones differed regarding Lewis antigen expression on N- and O-linked glycans as well as on GLs. Both clones examined supported adhesion of a Le(b)-binding H. pylori strain and may thus be a useful in vitro model system for H. pylori colonization/infection studies.

sted, utgiver, år, opplag, sider
2008. Vol. 18, nr 7, s. 494-501
Emneord [en]
Bacterial adhesion, fucosyltransferase, Helicobacter pylori, Lewis antigens
HSV kategori
Identifikatorer
URN: urn:nbn:se:umu:diva-22627DOI: 10.1093/glycob/cwn030PubMedID: 18400963Scopus ID: 2-s2.0-45749135061OAI: oai:DiVA.org:umu-22627DiVA, id: diva2:217432
Tilgjengelig fra: 2009-05-14 Laget: 2009-05-14 Sist oppdatert: 2023-03-24bibliografisk kontrollert
Inngår i avhandling
1. Helicobacter pylori: multitalented adaptation of binding properties
Åpne denne publikasjonen i ny fane eller vindu >>Helicobacter pylori: multitalented adaptation of binding properties
2012 (engelsk)Doktoravhandling, med artikler (Annet vitenskapelig)
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.

sted, utgiver, år, opplag, sider
Umeå: Umeå university, 2012. s. 52
Serie
Umeå University medical dissertations, ISSN 0346-6612 ; 1524
Emneord
Helicobacter pylori, adherence, receptor specificity, adaptation, pH, BabA, Leb, recombination, secretor phenotype, recombinant cell lines
HSV kategori
Identifikatorer
urn:nbn:se:umu:diva-60751 (URN)978-91-7459-487-4 (ISBN)
Disputas
2012-11-16, KB3A9, KBC-huset, Umeå, 09:00 (engelsk)
Opponent
Veileder
Tilgjengelig fra: 2012-10-26 Laget: 2012-10-25 Sist oppdatert: 2021-11-01bibliografisk kontrollert

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