title: Inhibition of the vacuolating and anion channel activities of the VacA toxin of Helicobacter pylori.
abstract: 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 plasma membrane 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.
authors.affiliation: Centro CNR Biomembrane, Dipartimento di Scienze Biomediche, Universita' di Padova, Viale G. Colombo 3, 35121, Padova, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Tombola
authors.forename: F
authors.initials: F
authors.lastname: Oregna
authors.forename: S
authors.initials: S
authors.lastname: Brutsche
authors.forename: I
authors.initials: I
authors.lastname: Szabò
authors.forename: G
authors.initials: G
authors.lastname: Del Giudice
authors.forename: R
authors.initials: R
authors.lastname: Rappuoli
authors.forename: C
authors.initials: C
authors.lastname: Montecucco
authors.forename: E
authors.initials: E
authors.lastname: Papini
authors.forename: M
authors.initials: M
authors.lastname: Zoratti
mesh_terms: D001426:Bacterial Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D018118:Chloride Channels / Q000037:antagonists & inhibitors; D004305:Dose-Response Relationship, Drug; D006367:HeLa Cells; D016480:Helicobacter pylori / Q000378:metabolism*; D006801:Humans; D020128:Inhibitory Concentration 50; D007473:Ion Channels / Q000378:metabolism; D008051:Lipid Bilayers / Q000378:metabolism; D018408:Patch-Clamp Techniques; D013997:Time Factors; D014617:Vacuoles / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D018118:Chloride Channels; D007473:Ion Channels; D008051:Lipid Bilayers; C074689:VacA protein, Helicobacter pylori