6533b86efe1ef96bd12cb4f3

RESEARCH PRODUCT

The Vibrio choleare haemolysin anion channel is required for cell vacuolation and death

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SummarySeveral strains of Vibrio cholerae secrete ahaemolytic toxin of 63kDa, termed V. cholerae cytolysin (VCC). This toxin causes extensive vacuo-lation and death of cells in culture and forms ananion-selective channel in planar lipid bilayers and incells. Here, we identify inhibitors of the VCC anionchannel and show that the formation of the anionchannel 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 com-partments and we identify the contribution of lateendosomes and of the trans -Golgi network in vacuolebiogenesis.Introduction The Gram-negative bacterium Vibrio cholerae is anintestinal non-invasive pathogen that adheres to theapical side of the small intestine (Salyers and Whitt, 1994)thereby inducing cholera, an acute watery diarrhoeadisease of humans (Kaper et al ., 1995). Vibrio cholerae produces several virulence factors that are involved in colonization and adhesion and also releases proteintoxins that co-operate to induce the alteration of ion andwater fluxes across the intestinal epithelium, which is thebasis of the massive loss of fluids characteristic of cholera(Kaper