The Vibrio cholerae haemolysin anion channel is required for cell vacuolation and death.
Several strains of Vibrio cholerae secrete a haemolytic toxin of 63 kDa, termed V. cholerae cytolysin (VCC). This toxin causes extensive vacuolation and death of cells in culture and forms an anion-selective channel in planar lipid bilayers and in cells. Here, we identify inhibitors of the VCC anion channel and show that the formation of the anion channel is necessary for the development of the vacuoles and for the cell death induced by this toxin. Using markers of cell organelles, we show that vacuoles derive from different intracellular compartments and we identify the contribution of late endosomes and of the trans-Golgi network in vacuole biogenesis.
Moschioni
Monica
M
Centro CNR Biomembrane and Dipartimento di Scienze Biomediche Sperimentali, Università di Padova, Via G. Colombo 3, 35121, Padova, Italy.
Tombola
Francesco
F
de Bernard
Marina
M
Coelho
Ana
A
Zitzer
Alexander
A
Zoratti
Mario
M
Montecucco
Cesare
C
D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid / Q000494:pharmacology; D012856:4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid / Q000494:pharmacology; D000643:Ammonium Chloride / Q000494:pharmacology; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001426:Bacterial Proteins; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D002460:Cell Line; D002522:Chlorocebus aethiops; D003603:Cytotoxins / Q000235:genetics / Q000633:toxicity; D011992:Endosomes / Q000502:physiology; D006056:Golgi Apparatus / Q000502:physiology; D006460:Hemolysin Proteins / Q000235:genetics / Q000633:toxicity*; D006801:Humans; D066298:In Vitro Techniques; D007473:Ion Channels / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology; D008051:Lipid Bilayers; D018942:Macrolides; D008954:Models, Biological; D014162:Transfection; D014617:Vacuoles / Q000187:drug effects / Q000502:physiology; D014709:Vero Cells; D014734:Vibrio cholerae / Q000235:genetics / Q000472:pathogenicity*
D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D003603:Cytotoxins; D006460:Hemolysin Proteins; D007473:Ion Channels; D008051:Lipid Bilayers; D018942:Macrolides; C073845:hemolysin, Vibrio; D000643:Ammonium Chloride; D012856:4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid; C040929:bafilomycin A1; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid