title: Helicobacter pylori cytotoxin VacA increases alkaline secretion in gastric epithelial cells.
abstract: Human infection by the bacterium Helicobacter pylori (Hp) may lead to severe 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 characterize the acute effects of VacA on the gastric epithelium. Our results show that VacA partially inhibits gastric acid output by increasing HCO(3)(-) efflux. Experiments conducted with double-barrelled pH or Cl(-)-selective microelectrodes on surface epithelial gastric cells (SECs) and single gastric glands show that VacA does not impair the activity of the oxyntic cells but renders the apical membrane of SECs more permeable to HCO(3)(-) and Cl(-). Inhibition of this permeation by 5-nitro-2-(3-phenylpropylamino) benzoic acid indicates that this may be due to the formation of anion-selective pores by the toxin. We suggest that VacA-dependent HCO(3)(-) efflux from SECs improves the environmental conditions (pH, CO(2) 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.
authors.affiliation: Dipartimento di Fisiologia Generale e Ambientale, Università di Bari, 70126 Bari, Italy. debellis@biologia.uniba.it
authors.forename: L
authors.initials: L
authors.lastname: Debellis
authors.forename: E
authors.initials: E
authors.lastname: Papini
authors.forename: R
authors.initials: R
authors.lastname: Caroppo
authors.forename: C
authors.initials: C
authors.lastname: Montecucco
authors.forename: S
authors.initials: S
authors.lastname: Curci
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000502:physiology / Q000633:toxicity*; D001639:Bicarbonates / Q000378:metabolism; D002463:Cell Membrane Permeability; D002712:Chlorides / Q000378:metabolism; D004847:Epithelial Cells / Q000502:physiology; D005744:Gastric Acid / Q000378:metabolism*; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism; D016480:Helicobacter pylori / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D008839:Microelectrodes; D011893:Rana esculenta
chemical_list: D001426:Bacterial Proteins; D001639:Bicarbonates; D002712:Chlorides; C074689:VacA protein, Helicobacter pylori