Signal transduction-mediated adherence and entry of Helicobacter pylori into cultured cells

Background & Aims: An ability to invade host cells could be a means for Hel icobacter pylori to achieve resistance to antibiotic therapy. The aim of th is study was to investigate the mechanisms involved in adherence and entry of H. pylori into cultured cells. Methods: Coinfection with Yersinia expres sing mutant or wild-type YopH tyrosine phosphatase was used. Genistein and cytochalasin D were used as inhibitors of adherence and entry; entry was mo nitored by a gentamicin-protection assay. Target cells were AGS cells and a beta 1-integrin-deficient cell line with its corresponding beta 1-integrin -expressing transfectant. Results: H. pylori induced phosphorylation of 125 -130-kilodalton proteins, similar in size to the target proteins of Yersini a YopH. Adherence of H. pylori was inhibited by Yersinia organisms expressi ng enzymatically active YopH but not by inactive YopH, Adherence and entry of H. pylori was considerably higher with beta 1-integrin-transfected cells than with beta 1-integrin-deficient cells, Antibodies directed against alp ha 5- and beta 1-integrin chains reduced adherence to the alpha 5 beta 1-in tegrin-expressing gastric cell line AGS. Entry was inhibited by both cytoch alasin D and genistein, Entry, but not adherence, was higher for 2 type I s trains than for a type II isolate. Conclusions: Invasion of gastric epithel ium via an integrin-mediated pathway could contribute to the ability of H. pylori to establish persistent infection.