Pathogenicity island-dependent activation of Rho GTPases Rac1 and Cdc42 inHelicobacter pylori infection

Helicobacter pylori has been identified as the major aetiological agent in the development of chronic gastritis and duodenal ulcer, and it plays a rol e in the development of gastric carcinoma. Attachment of H. pylori to gastr ic epithelial cells leads to nuclear and cytoskeletal responses in host cel ls. Here, we show that Rho GTPases Rad and Cdc42 were activated during infe ction of gastric epithelial cells with either the wild-type H. pylori or th e mutant strain cagA. In contrast, no activation of Rho GTPases was observe d when H. pylori mutant strains (virB7 and PAI) were used that lack functio nal type IV secretion apparatus. We demonstrated that H. pylori-induced act ivation of Rad and Cdc42 led to the activation of p21-activated kinase 1 (P AK1) mediating nuclear responses, whereas the mutant strain PAI had no effe ct on PAK1 activity. Activation of Rad, Cdc42 and PAK1 represented a very e arly event in colonization of gastric epithelial cells by H. pylori. Rad an d Cdc42 were recruited to the sites of bacterial attachment and are therefo re probably involved in the regulation of local and overall cytoskeleton re arrangement in host cells. Finally, actin rearrangement and epithelial cell motility in H. pylori infection depended on the presence of a functional t ype IV secretion system encoded by the cag pathogenicity island (PAI).