Helicobacter pylori SabA adhesin in persistent infection and chronic inflammation.
Journal: 2002/August - Science
ISSN: 1095-9203
Abstract:
Helicobacter pylori adherence in the human gastric mucosa involves specific bacterial adhesins and cognate host receptors. Here, we identify sialyl-dimeric-Lewis x glycosphingolipid as a receptor for H. pylori and show that H. pylori infection induced formation of sialyl-Lewis x antigens in gastric epithelium in humans and in a Rhesus monkey. The corresponding sialic acid-binding adhesin (SabA) was isolated with the "retagging" method, and the underlying sabA gene (JHP662/HP0725) was identified. The ability of many H. pylori strains to adhere to sialylated glycoconjugates expressed during chronic inflammation might thus contribute to virulence and the extraordinary chronicity of H. pylori infection.
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Science 297(5581): 573-578

<em>Helicobacter pylori</em> SabA Adhesin in Persistent Infection and Chronic Inflammation

+14 authors
Department of Odontology/Oral Microbiology, Umeå University, SE-901 87 Umeå, Sweden.
The Swedish Institute for Infectious Disease Control, SE-171 82 Solna, Sweden.
Institute of Medical Biochemistry, Göteborg University, Box 440, SE-405 30 Göteborg, Sweden.
Institute of Molecular and Cell Biology, Tartu University, EE-51010 Tartu, Estonia.
Department of Infectious Diseases and Medical Microbiology, Lund University, SE-223 62 Lund, Sweden.
Department of Molecular Microbiology, Washington University Medical School, St. Louis, MO 63110, USA.
Laboratory of Gastrointestinal and Liver Studies, Department of Medicine, USUHS, Bethesda, MD 20814–4799, USA.
Department of Molecular and Clinical Medicine, Division of Medical Microbiology, Linköping University, SE-581 85 Linköping, Sweden.
Department of Chemistry, Swedish University of Agricultural Sciences, SE-750 07 Uppsala, Sweden.
IsoSep AB, Dalkärrsv. 11, SE-146 36 Tullinge, Sweden.
Department of Medical Biosciences/Clinical Cytology, Umeå University, SE-901 87 Umeå, Sweden.
Department of Molecular Biology, Umeå University, SE-901 87 Umeå, Sweden.
Center for Biotechnology, Karolinska Institute, Novum, SE-141 57 Huddinge, Sweden.
These authors contributed equally to this work.
Present address: Unité de Génétique Mycobactérienne, Institut Pasteur, 25 rue du Dr Roux, 75724 Paris Cedex 15, France.
To whom correspondence should be addressed. E-mail: es.umu.tnodo@neroB.samohT

Abstract

Helicobacter pylori adherence in the human gastric mucosa involves specific bacterial adhesins and cognate host receptors. Here, we identify sialyl-dimeric-Lewis × glycosphingolipid as a receptor for H. pylori and show that H. pylori infection induced formation of sialyl-Lewis × antigens in gastric epithelium in humans and in a Rhesus monkey. The corresponding sialic acid–binding adhesin (SabA) was isolated with the “retagging” method, and the underlying sabA gene (JHP662/HP0725) was identified. The ability of many H. pylori strains to adhere to sialylated glycoconjugates expressed during chronic inflammation might thus contribute to virulence and the extraordinary chronicity of H. pylori infection.

Abstract

Helicobacter pylori persistently infects the gastric mucosa of more than half of all people worldwide, causes peptic ulcer disease, and is an early risk factor for gastric cancer (1). Many H. pylori strains express adhesin proteins that bind to specific host-cell macromolecule receptors (2). This adherence may be advantageous to H. pylori by helping to stabilize it against mucosal shedding into the gastric lumen and ensuring good access to nourishing exudate from gastric epithelium that has been damaged by the infection. The best defined H. pylori adhesin-receptor interaction found to date is that between the Leb blood group antigen binding adhesin, BabA, a member of a family of H. pylori outer membrane proteins, and the H, Lewis b (Leb), and related ABO antigens (3-5). These fucose-containing blood group antigens are found on red blood cells and in the gastrointestinal mucosa (6). Blood group–O individuals suffer disproportionately from peptic ulcer disease, suggesting that bacterial adherence to the H and Leb antigens affects the severity of infection (7). Additional H. pylori–host macromolecule interactions that do not involve Leb-type antigens have also been reported (8).

H. pylori is a genetically diverse species, with strains differing markedly in virulence. Strains from persons with overt disease generally carry the cag-pathogenicity island (cag-PAI) (9, 10), which mediates translocation of CagA into host cells, where it is tyrosine phosphorylated and affects host cell signaling (11). Leb antigen binding is most prevalent among cag strains from persons with overt disease (4, 12). Separate studies using transgenic mice that express the normally absent Leb antigen suggest that H. pylori adherence exacerbates inflammatory responses in this model (13). Taken together, these results point to the pivotal role of H. pylori adherence in development of severe disease.

Footnotes

Supporting Online Material

www.sciencemag.org/cgi/content/full/297/5581/573/DC1

Materials and Methods

Figs. S1 and S2

Tables S1 and S2

Footnotes

References and Notes

References and Notes

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