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 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.
Tombola
F
F
Centro CNR Biomembrane, Dipartimento di Scienze Biomediche, Universita' di Padova, Viale G. Colombo 3, 35121, Padova, Italy.
Oregna
F
F
Brutsche
S
S
Szabò
I
I
Del Giudice
G
G
Rappuoli
R
R
Montecucco
C
C
Papini
E
E
Zoratti
M
M
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
D001426:Bacterial Proteins; D018118:Chloride Channels; D007473:Ion Channels; D008051:Lipid Bilayers; C074689:VacA protein, Helicobacter pylori