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- Aspholm-Hurtig, Marina, et al.
(author)
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Functional adaptation of BabA, the H. pylori ABO blood group antigen binding adhesin.
- 2004
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In: Science (New York, N.Y.). - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 305:5683, s. 519-22
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Journal article (peer-reviewed)abstract
- Adherence by Helicobacter pylori increases the risk of gastric disease. Here, we report that more than 95% of strains that bind fucosylated blood group antigen bind A, B, and O antigens (generalists), whereas 60% of adherent South American Amerindian strains bind blood group O antigens best (specialists). This specialization coincides with the unique predominance of blood group O in these Amerindians. Strains differed about 1500-fold in binding affinities, and diversifying selection was evident in babA sequences. We propose that cycles of selection for increased and decreased bacterial adherence contribute to babA diversity and that these cycles have led to gradual replacement of generalist binding by specialist binding in blood group O-dominant human populations.
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| 2. |
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| 3. |
- Lindén, Sara
(author)
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Helicobacter pylori binding to gastric mucins and host glycosylation changes after inoculation
- 2004
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Doctoral thesis (other academic/artistic)abstract
- Helicobacter pylori may cause gastritis, gastric/duodenal ulcer and gastric cancer. During infection, most H. pylori are found in the gastric mucus layer, but some are attached to, or have penetrated, epithelial cells. The aim of this study is to characterize the binding of H. pylori to gastric mucins and to investigate host changes that occur after inoculation. Results: H. pylori binds to mucins by at least 3 different mechanisms: 1) to host Leb and related structures via the BabA adhesin, 2) to host sialyl-Lex via the SabA adhesin and 3) to sialylated host structures at low pH. H. pylori strains expressing the BabA adhesin bind to the human MUC5AC mucin via Leb and to a gastric low-molecular-mass mucin-like molecule (possibly MUC1) via the H-type-1 structure. Leb-positive MUC5AC glycoforms differed in their receptor properties for different H. pylori strains. At pH 3, Leb binding was abolished, although all strains bound to a proteoglycan containing chondroitin sulfate/dermatan sulfate chains, to a component behaving as a monomeric mucin of higher charge and larger size than the subunits of MUC5AC/MUC6, and to a highly charged MUC5AC glycoform. Rhesus monkey and human gastric mucins are similar with respect to tissue localization, size, density, glycoforms, terminal carbohydrate substitution and H. pylori binding. After H. pylori inoculation, 8 of 10 monkeys developed persistent infection accompanied by gastritis. muc5AC and muc6 localized to the mucous cells of the surface epithelium and to the glands respectively, and no muc2 or sulfo-mucins were detected during the 10-month period investigated. A transient increase in sialylated Lewis antigens occurred as early as one week after inoculation. Furthermore, Lea and/or Leb expression briefly decreased in 5/7 Leb-positive animals, but later tended to increase, and in Lea/Leb negative animals Lea and/or Leb increased to a variable extent. H. pylori adherence in vitro reflects these glycosylation changes in that an increased binding with a sialyl-Lex binding strain, and an initial decrease in adherence by a Leb-binding one were observed, suggesting that the SabA and BabA adhesins play complementary roles during infection. Conclusions: H. pylori binding to mucins at neutral pH is strain, blood-group and glycoform dependent whereas binding at acidic pH seems to be a common feature for all strains. The host responds rapidly to bacterial challenge by changing the expression of carbohydrate structures used by the microbe for adhesion.
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| 4. |
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| 5. |
- Lindén, Sara, et al.
(author)
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Strain- and blood group-dependent binding of Helicobacter pylori to human gastric MUC5AC glycoforms.
- 2002
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In: Gastroenterology. - : Elsevier BV. - 1528-0012 .- 0016-5085. ; 123:6, s. 1923-1930
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Journal article (peer-reviewed)abstract
- Background & Aims: In the stomach, Helicobacter pylori is found both in the mucus layer and adhering to the gastric epithelium. The aim of this study is to characterize the binding of H. pylori to human gastric mucins. Methods:H. pylori strains that bind the Lewisb (Leb) structure (via the BabA adhesin) and/or sialylated structures, along with isogenic adhesion deletion mutants, were used to identify microbe-binding mucins. Gastric mucins from 5 healthy individuals, isolated by density-gradient centrifugation, were investigated for H. pylori binding at neutral pH using a microtiter-based technique. Results:H. pylori strains that express the BabA adhesins were shown to bind to the MUC5AC mucin in individuals expressing the Leb antigen. Further fractionation with an ion-exchange chromatography revealed Leb-positive MUC5AC glycoforms that differed in their receptor properties for different H. pylori strains. None of the H. pylori strains studied bound to mucins from Leb-negative individuals. However, all strains bound to low-density, nonmucin, Leb-negative material on top of the gradients. Conclusions: Binding of H. pylori to human gastric MUC5AC isolated from healthy individuals is BabA dependent and mediated by the Leb structure presented by the mucin. However, the BabA adhesins demonstrate strain-dependent preference in binding to MUC5AC glycoforms substituted with Leb, allowing for great interindividual variability in host–microbe interactions.
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