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Functional adaptation of BabA, the H. pylori ABO blood group antigen binding adhesin
Umeå University, Faculty of Medicine, Department of Odontology, Oral Microbiology.
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2004 (English)In: Science, ISSN 0036-8075, E-ISSN 1095-9203, Vol. 305, no 5683, p. 519-522Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
American Association for the Advancement of Science , 2004. Vol. 305, no 5683, p. 519-522
Keywords [en]
ABO Blood-Group System/*metabolism, Adaptation; Biological, Adhesins; Bacterial/chemistry/*genetics/immunology/*metabolism, Alleles, Bacterial Adhesion, Base Sequence, Binding Sites, Evolution; Molecular, Fucose/metabolism, Gastric Mucosa/microbiology, Helicobacter Infections/microbiology, Helicobacter pylori/genetics/immunology/*physiology, Humans, Indians; South American, Lewis Blood-Group System/metabolism, Molecular Sequence Data, Mutation, Peru, Phenotype, Phylogeny, Protein Binding, Selection (Genetics), Transformation; Bacterial
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: urn:nbn:se:umu:diva-6649DOI: 10.1126/science.1098801ISI: 000222828900040PubMedID: 15273394Scopus ID: 2-s2.0-3242748894OAI: oai:DiVA.org:umu-6649DiVA, id: diva2:146319
Available from: 2008-01-08 Created: 2008-01-08 Last updated: 2023-03-23Bibliographically approved
In thesis
1. Adaptation of Helicobacter pylori Adherence Properties in Promotion of Host Tropism and Inflammatory Disease
Open this publication in new window or tab >>Adaptation of Helicobacter pylori Adherence Properties in Promotion of Host Tropism and Inflammatory Disease
2004 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Being among the most prevalent of persistent infectious agents in humans worldwide, Helicobacter pylori induces chronic inflammation (gastritis), which may progress to peptic ulceration and stomach cancer. The ability to adhere to the gastric mucosa is considered to be both a colonization and virulence property of H. pylori. For adherence, H. pylori expresses surface-located attachment proteins (adhesins) that bind to specific receptors in the gastric mucosa. The best characterized H. pylori adhesin-receptor interaction is that between the blood group antigen binding adhesin (BabA) and the fucosylated blood group antigens, which are glycans highly expressed in the gastric mucosa.

Our recent results have changed the view of the blood group antigen-specific binding mode of H. pylori. We have tested clinical isolates of H. pylori from human populations worldwide for their ability to bind to ABO blood group antigens. The results revealed that more than 95% of isolates from Sweden, Germany, Spain, Japan and Alaska that bind fucosylated blood group antigens, bind both the Lewis b antigen (Leb) (of blood group O) and the blood group A-related antigen A-Lewis b, i.e. they exhibit a generalist type of binding mode. In contrast, the majority of strains (62%) from South American Amerindians bound best to Leb, i.e. they exhibit a specialist blood group “O antigen” binding mode. This specialization in binding coincides with the unique predominance of blood group O in the South American Amerindian populations. Furthermore, we also showed that H. pylori could switch from specialist to generalist binding modes by chromosomal integration of foreign babA gene fragments.

A mutant strain lacking the babA gene turned out to adhere to inflamed gastric epithelium, despite the fact that it did not bind Leb. We identified the receptor to which the mutant binds to as the sialyl-dimeric-Lewis x antigen (sdiLex) and found its expression to be associated with persistent H. pylori infection and chronic inflammation, both in humans and Rhesus monkeys. The cognate sialic acid binding adhesin (SabA) was identified by our ReTagging technique. Deletion of sabA caused loss of H. pylori binding to sialylated glycans, and screening of single colony isolates revealed a high frequency of spontaneous on⇒off phase variation in sLex binding.

Using erythrocytes as a model for sialyl dependent cell adhesion, we could show that SabA is the sought-after H. pylori sialyl-dependent hemagglutinin. Swedish clinical H. pylori isolates were analyzed for sialyl-dependent hemagglutination (sia-HA), and the sia-HA titers were found to be highly correlated to the levels of sLex binding. Clinical isolates were shown to exhibit several distinct binding modes for sialylated glycans, which suggest that SabA exhibit polymorphism in binding. We also found that SabA binds to sialylated glycans on neutrophil surfaces by mechanisms involving “selectin mimicry”, and that SabA plays an important role in nonopsonic activation of neutrophils.

In the human stomach, H. pylori is exposed to selective pressures such as immune and inflammatory responses, and this is reflected by changes in mucosal glycosylation patterns. The high mutation and recombination rates of H. pylori in combination with bio selection will continuously generate clones that are adapted to changes in individual gastric mucosa. Such adaptive selection contributes to the remarkable diversity in binding modes and to the extraordinary chronicity of H. pylori infections worldwide.

Publisher
p. 68
Series
Umeå University medical dissertations, ISSN 0346-6612 ; 87
Keywords
H. pylori, BabA, SabA, adhesin, blood group antigens, sialylated, phase variation, hemagglutination, selectin, adaptation
Research subject
Odontology
Identifiers
urn:nbn:se:umu:diva-388 (URN)91-7305-736-3 (ISBN)
Public defence
2004-11-30, KB3A9, KBC-huset, Umeå, 13:00 (English)
Opponent
Available from: 2004-12-21 Created: 2004-12-21 Last updated: 2009-12-08Bibliographically approved

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Vikström, SusanneSjöström, RolfBäckström, AnnaArnqvist, AnnaBorén, Thomas

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Vikström, SusanneSjöström, RolfBäckström, AnnaArnqvist, AnnaBorén, Thomas
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Microbiology in the medical areaMedical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)

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