Inhibition of the vacuolating and anion channel activities of the VacA toxin of Helicobacter pylori

VacA, the vacuolating cytotoxin secreted by Helicobacter pylori, is believed to be a major causative factor in the development of gastroduodenal ulcers, This toxin causes vacuolation of cultured cells and it has recently been found to form anion-selective channels upon insertion into planar bilayers as well as in the plasmamembrane of HeLa cells. Here, we identify a series of inhibitors of VacA channels and we compare their effectiveness as channel blockers and as inhibitors of VacA-induced vacuolation, confirming that the two phenomena are linked, This characterization opens the way to studies in other experimental systems and to the search for a specific inhibitor of VacA action. (C) 1999 Federation of European Biochemical Societies.