Helicobacter pylori cytotoxin VacA increases alkaline secretion in gastricepithelial cells

Human infection by the bacterium Helicobacter pylori (Hp) may lead to sever e gastric diseases by an ill-understood process involving several virulence factors. Among these, the cytotoxin VacA is associated with higher tissue damage. In this study, the isolated frog stomach model was used to characte rize the acute effects of VacA on the gastric epithelium. Our results show that VacA partially inhibits gastric acid output by increasing HCO3- efflux . Experiments conducted with double-barrelled pH or Cl--selective microelec trodes on surface epithelial gastric cells (SECs) and single gastric glands show that VacA does not impair the activity of the oxyntic cells but rende rs the apical membrane of SECs more permeable to HCO3- and Cl-. Inhibition of this permeation by 5-nitro-2-(3-phenylpropylamino) benzoic acid indicate s that this may be due to the formation of anion-selective pores by the tox in. We suggest that VacA-dependent HCO3- efflux from SECs improves the envi ronmental conditions (pH, CO2 concentration) of the niche parasitized by Hp , that is the gastric surface. This may favor Hp persistence in the tissue and the secondary development of a chronic inflammation.