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BETA
Henriksson, Sara
Alternative names
Publications (8 of 8) Show all publications
Bugaytsova, J. A., Björnham, O., Chernov, Y. A., Gideonsson, P., Henriksson, S., Mendez, M., . . . Boren, T. (2017). Helicobacter pylori Adapts to Chronic Infection and Gastric Disease via pH-Responsive BabA-Mediated Adherence. Cell Host and Microbe, 21(3), 376-389
Open this publication in new window or tab >>Helicobacter pylori Adapts to Chronic Infection and Gastric Disease via pH-Responsive BabA-Mediated Adherence
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2017 (English)In: Cell Host and Microbe, ISSN 1931-3128, E-ISSN 1934-6069, Vol. 21, no 3, p. 376-389Article in journal (Refereed) Published
Abstract [en]

The BabA adhesin mediates high-affinity binding of Helicobacter pylori to the ABO blood group antigen-glycosylated gastric mucosa. Here we show that BabA is acid responsive-binding is reduced at low pH and restored by acid neutralization. Acid responsiveness differs among strains; often correlates with different intragastric regions and evolves during chronic infection and disease progression; and depends on pH sensor sequences in BabA and on pH reversible formation of high-affinity binding BabA multimers. We propose that BabA's extraordinary reversible acid responsiveness enables tight mucosal bacterial adherence while also allowing an effective escape from epithelial cells and mucus that are shed into the acidic bactericidal lumen and that bio-selection and changes in BabA binding properties through mutation and recombination with babA-related genes are selected by differences among individuals and by changes in gastric acidity over time. These processes generate diverse H. pylori subpopulations, in which BabA's adaptive evolution contributes to H. pylori persistence and overt gastric disease.

Place, publisher, year, edition, pages
CELL PRESS, 2017
National Category
Microbiology in the medical area Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Identifiers
urn:nbn:se:umu:diva-132788 (URN)10.1016/j.chom.2017.02.013 (DOI)000396375600023 ()28279347 (PubMedID)
Available from: 2017-05-11 Created: 2017-05-11 Last updated: 2019-05-24Bibliographically approved
Francis, M. K., Holst, M. R., Vidal-Quadras, M., Henriksson, S., Santarella-Mellwig, R., Sandblad, L. & Lundmark, R. (2015). Endocytic membrane turnover at the leading edge is driven by a transient interaction between Cdc42 and GRAF1. Journal of Cell Science, 128(22), 4183-4195
Open this publication in new window or tab >>Endocytic membrane turnover at the leading edge is driven by a transient interaction between Cdc42 and GRAF1
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2015 (English)In: Journal of Cell Science, ISSN 0021-9533, E-ISSN 1477-9137, Vol. 128, no 22, p. 4183-4195Article in journal (Refereed) Published
Abstract [en]

Changes in cell morphology require coordination of plasma membrane turnover and cytoskeleton dynamics, processes that are regulated by Rho GTPases. Here, we describe how a direct interaction between the Rho GTPase Cdc42 and the GTPase activating protein (GAP) GRAF1, facilitate rapid cell surface turnover at the leading edge. Both Cdc42 and GRAF1 were required for fluid phase uptake and regulated the generation of transient GRAF1-coated endocytic carriers, distinct from clathrin coated vesicles. GRAF1 was found to transiently assemble at discrete Cdc42-enriched punctae at the plasma membrane resulting in a corresponding decrease in Cdc42 microdomain association. However, Cdc42 captured in its active state was, via a GAP domain mediated interaction, localised together with GRAF1 on accumulated internal structures derived from the cell surface. Correlative fluorescence and electron tomography microscopy revealed that these structures were clusters of small membrane carriers affected in their endosomal processing. We conclude that a transient interaction between Cdc42 and GRAF1 drives endocytic turnover and controls the transition essential for endosomal maturation of plasma membrane internalised by this mechanism.

National Category
Biochemistry and Molecular Biology Cell Biology
Research subject
Medical Biochemistry
Identifiers
urn:nbn:se:umu:diva-111228 (URN)10.1242/jcs.174417 (DOI)000366314900017 ()26446261 (PubMedID)
Available from: 2015-11-11 Created: 2015-11-10 Last updated: 2018-06-07Bibliographically approved
Henriksson, S. (2012). Helicobacter pylori: multitalented adaptation of binding properties. (Doctoral dissertation). Umeå: Umeå university
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. p. 52
Series
Umeå University medical dissertations, ISSN 0346-6612 ; 1524
Keywords
Helicobacter pylori, adherence, receptor specificity, adaptation, pH, BabA, Leb, recombination, secretor phenotype, recombinant cell lines
National Category
Microbiology in the medical area
Identifiers
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)
Opponent
Supervisors
Available from: 2012-10-26 Created: 2012-10-25 Last updated: 2018-06-08Bibliographically approved
Azevedo, M., Eriksson, S., Mendes, N., Serpa, J., Figueiredo, C., Resende, L., . . . David, L. (2008). Infection by Helicobacter pylori expressing the BabA adhesin is influenced by the secretor phenotype. Journal of Pathology, 215(3), 308-316
Open this publication in new window or tab >>Infection by Helicobacter pylori expressing the BabA adhesin is influenced by the secretor phenotype
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2008 (English)In: Journal of Pathology, ISSN 0022-3417, E-ISSN 1096-9896, Vol. 215, no 3, p. 308-316Article 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.

Keywords
Helicobacter pylori; blood-group antigen binding adhesin (BabA); Lewis antigens; secretor status; gastritis; intestinal metaplasia; stomach; immunofluorescence
National Category
Microbiology in the medical area
Identifiers
urn:nbn:se:umu:diva-22412 (URN)10.1002/path.2363 (DOI)18498114 (PubMedID)
Available from: 2009-05-07 Created: 2009-05-07 Last updated: 2018-06-08Bibliographically approved
Löfling, J., Diswall, M., Eriksson, S., Borén, T., Breimer, M. E. & Holgersson, J. (2008). Studies of Lewis antigens and H. pylori adhesion in CHO cell lines engineered to express Lewis b determinants. Glycobiology, 18(7), 494-501
Open this publication in new window or tab >>Studies of Lewis antigens and H. pylori adhesion in CHO cell lines engineered to express Lewis b determinants
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2008 (English)In: Glycobiology, ISSN 0959-6658, E-ISSN 1460-2423, Vol. 18, no 7, p. 494-501Article in journal (Refereed) 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.

Keywords
Bacterial adhesion, fucosyltransferase, Helicobacter pylori, Lewis antigens
National Category
Microbiology in the medical area
Identifiers
urn:nbn:se:umu:diva-22627 (URN)10.1093/glycob/cwn030 (DOI)18400963 (PubMedID)
Available from: 2009-05-14 Created: 2009-05-14 Last updated: 2018-06-08Bibliographically approved
Nordén, J., Westermark, M., Bugaytsova, J., Mendez, A., Henriksson, S. & Borén, T.Characterization of BabA independent binding activity for ABO blood group antigens by Helicobacter pylori.
Open this publication in new window or tab >>Characterization of BabA independent binding activity for ABO blood group antigens by Helicobacter pylori
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(English)Manuscript (preprint) (Other academic)
National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Identifiers
urn:nbn:se:umu:diva-56319 (URN)
Available from: 2012-06-14 Created: 2012-06-14 Last updated: 2018-06-08Bibliographically approved
Henriksson, S., Mendez, M., Bugaytsova, J., Brännström, K., Nordén, J., Berg, D. E., . . . Borén, T.Clinical isolates of Helicobacter pylori demonstrates alternative BabA-mediated adherence to human gastric mucosa.
Open this publication in new window or tab >>Clinical isolates of Helicobacter pylori demonstrates alternative BabA-mediated adherence to human gastric mucosa
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(English)Manuscript (preprint) (Other academic)
Abstract [en]

Helicobacter pylori infection is life-long and can cause peptic ulcer disease and gastric cancer. The H. pylori BabA adhesin binds the ABO/Leb blood group (bg) antigens (Leb), which mediates attachment to the gastric epithelium. The prevalence of ABO binding is high worldwide and also in northern Europe. However, prevalence is reduced by 50% in Germany and is further reduced in Spain and Portugal. An inventory of strains from different European populations resulted in strains with high level of BabA expression but very little or no binding to Leb. The majority of such strains could not bind to human gastric mucosa in vitro. We further characterized a Spanish isolates, strain 812, that binds only weakly to soluble Leb-conjugate but still adheres firmly to gastric mucosa indicative of that it might bind to an alternative set of receptor. Receptor analysis by glycan arrays revealed higher binding of strain 812 to ALeb and Bleb glycans than to Leb, indicating that BabA from strain 812 has shifted its binding epitope somewhat away from the central Fuca1.2Gal bg domain and closer to the very terminal bg A and B determinants, i.e. GalNAca1.3Gal (bgA) or the Gala1.3Gal (bgB). By a colony screening approach we identified a subpopulation of 812 clones adapted for stronger Leb binding. Such affinity shifts comes from replacement of distinguishing amino acids by mechanisms of recombination with a BabA-related outer membrane protein.

Keywords
Adhesion, recombination, adaptation
National Category
Microbiology in the medical area
Identifiers
urn:nbn:se:umu:diva-60724 (URN)
Available from: 2012-10-25 Created: 2012-10-24 Last updated: 2018-06-08Bibliographically approved
Bugaytsova, J., Björnhamn, O., Henriksson, S., Johansson, P., Mendez, M., Sjöström, R., . . . Borén, T. pH regulated H. pylori adherence: implications for persistent infection and disease.
Open this publication in new window or tab >>pH regulated H. pylori adherence: implications for persistent infection and disease
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(English)Manuscript (preprint) (Other academic)
Abstract [en]

Helicobacter pylori’s BabA adhesin binds strongly to gastric mucosal ABH/Leb glycans on the stomach epithelium and overlying mucus, materials continuously shed into the acidic gastric lumen. Here we report that this binding is acid labile, acid inactivation is fully reversible; and acid lability profiles vary with BabA sequence and correlate with disease patterns. Isogenic H. pylori strains from the gastric antrum and more acidic corpus were identified that differed in acid lability of receptor binding and in sequence near BabA’s carbohydrate binding domain. We propose that reversible acid inactivation of receptor binding helps H. pylori avoid clearance by mucosal shedding, and that strain differences in acid lability affect tissue tropism and the spectrum of associated gastric diseases.

National Category
Microbiology in the medical area
Identifiers
urn:nbn:se:umu:diva-21487 (URN)
Available from: 2009-04-14 Created: 2009-04-14 Last updated: 2018-06-09Bibliographically approved
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