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BabA-mediated adherence is a potentiator of the Helicobacter pylori type IV secretion system activity
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2011 (English)In: Journal of Biological Chemistry, ISSN 0021-9258, E-ISSN 1083-351X, Vol. 286, no 28, 25256-25264 p.Article in journal (Refereed) Published
Abstract [en]

Chronic infection of Helicobacter pylori in the stomach mucosa with translocation of the bacterial cytotoxin-associated gene A (CagA) effector protein via the cag-Type IV secretion system (TFSS) into host epithelial cells are major risk factors for gastritis, gastric ulcers, and cancer. The blood group antigen-binding adhesin BabA mediates the adherence of H. pylori to ABO/Lewis b (Le(b)) blood group antigens in the gastric pit region of the human stomach mucosa. Here, we show both in vitro and in vivo that BabA-mediated binding of H. pylori to Le(b) on the epithelial surface augments TFSS-dependent H. pylori pathogenicity by triggering the production of proinflammatory cytokines and precancer-related factors. We successfully generated Le(b)-positive cell lineages by transfecting Le(b)-negative cells with several glycosyltransferase genes. Using these established cell lines, we found increased mRNA levels of proinflammatory cytokines (CCL5 and IL-8) as well as precancer-related factors (CDX2 and MUC2) after the infection of Le(b)-positive cells with WT H. pylori but not with babA or TFSS deletion mutants. This increased mRNA expression was abrogated when Le(b)-negative cells were infected with WT H. pylori. Thus, H. pylori can exploit BabA-Le(b) binding to trigger TFSS-dependent host cell signaling to induce the transcription of genes that enhance inflammation, development of intestinal metaplasia, and associated precancerous transformations.

Place, publisher, year, edition, pages
2011. Vol. 286, no 28, 25256-25264 p.
National Category
Cell and Molecular Biology Biochemistry and Molecular Biology
URN: urn:nbn:se:umu:diva-82539DOI: 10.1074/jbc.M111.233601ISI: 000292547900071PubMedID: 21596743OAI: diva2:661813
Available from: 2013-11-05 Created: 2013-11-05 Last updated: 2014-04-23Bibliographically approved

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Borén, Thomas
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Department of Medical Biochemistry and Biophysics
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