title: Vacuolation induced by VacA toxin of Helicobacter pylori requires the intracellular accumulation of membrane permeant bases, Cl(-) and water.
abstract: The protein vacuolating toxin A (VacA) of Helicobacter pylori converts late endosomes into large vacuoles in the presence of permeant bases. Here it is shown that this phenomenon corresponds to an accumulation of permeant bases and Cl(-) in HeLa cells and requires the presence of extracellular Cl(-). The net influx of Cl(-) is due to electroneutral, Na(+), K(+), 2Cl(-) cotransporter-mediated transport. Cell vacuolation leads to cell volume increase, consistent with water flux into the cell, while hyper-osmotic media decreased vacuole formation. These data represent the first evidence that VacA-treated cells undergo an osmotic unbalance, reinforcing the hypothesis that the VacA chloride channel is responsible for cell vacuolation.
authors.affiliation: Centro CNR Biomembrane, Department of Biomedical Sciences, University of Padova, Padua, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Morbiato
authors.forename: F
authors.initials: F
authors.lastname: Tombola
authors.forename: S
authors.initials: S
authors.lastname: Campello
authors.forename: G
authors.initials: G
authors.lastname: Del Giudice
authors.forename: R
authors.initials: R
authors.lastname: Rappuoli
authors.forename: M
authors.initials: M
authors.lastname: Zoratti
authors.forename: E
authors.initials: E
authors.lastname: Papini
mesh_terms: D000643:Ammonium Chloride / Q000494:pharmacology; D001426:Bacterial Proteins / Q000378:metabolism / Q000633:toxicity*; D002034:Bumetanide / Q000494:pharmacology; D002463:Cell Membrane Permeability; D048429:Cell Size; D002712:Chlorides / Q000378:metabolism*; D011992:Endosomes / Q000378:metabolism; D006367:HeLa Cells; D016480:Helicobacter pylori; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008744:Methylamines / Q000378:metabolism; D009997:Osmotic Pressure; D049994:Sodium Potassium Chloride Symporter Inhibitors; D028021:Sodium-Potassium-Chloride Symporters / Q000378:metabolism; D014617:Vacuoles / Q000187:drug effects / Q000378:metabolism*; D014867:Water / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D002712:Chlorides; D008744:Methylamines; D049994:Sodium Potassium Chloride Symporter Inhibitors; D028021:Sodium-Potassium-Chloride Symporters; C074689:VacA protein, Helicobacter pylori; D000643:Ammonium Chloride; D014867:Water; D002034:Bumetanide; C027451:methylamine