title: BabA-mediated adherence is a potentiator of the Helicobacter pylori type IV secretion system activity.
abstract: 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.
authors: Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
authors: Nozomi
authors: N
authors: Ishijima
authors: Masato
authors: M
authors: Suzuki
authors: Hiroshi
authors: H
authors: Ashida
authors: Yusuke
authors: Y
authors: Ichikawa
authors: Yumi
authors: Y
authors: Kanegae
authors: Izumu
authors: I
authors: Saito
authors: Thomas
authors: T
authors: Borén
authors: Rainer
authors: R
authors: Haas
authors: Chihiro
authors: C
authors: Sasakawa
authors: Hitomi
authors: H
authors: Mimuro
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