Vacuolation induced by VacA toxin of Helicobacter pylori requires the intracellular accumulation of membrane permeant bases, Cl- and water

The protein vacuolating toxin A (VacA) of Helicobacter pylori converts late endosomes into large vacuoles in the presence of permeant bases. Here it i s shown that this phenomenon corresponds to an accumulation of permeant bas es and Cl- in HeLa cells and requires the presence of extracellular Cl-. Th e net influx of Cl- is due to electroneutral, Na+, K+, 2Cl(-) cotransporter -mediated transport. Cell vacuolation leads to cell volume increase, consis tent with water flux into the cell, while hyper-osmotic media decreased vac uole formation. These data represent the first evidence that VacA-treated c ells undergo an osmotic unbalance, reinforcing the hypothesis that the VacA chloride channel is responsible for cell vacuolation. (C) 2001 Published b y Elsevier Science B.V. on behalf of the Federation of European Biochemical Societies.