The vacuolar ATPase proton pump is required for the cytotoxicity of Bacillus anthracis lethal toxin.
The nature of the cytopathic effect exerted by the lethal factor toxin (LF) of Bacillus anthracis on sensitive cells is unknown. The toxin requires the passage through acidic vesicles in order to exert its effect within the cytosol. Here, we show that bafilomycins and concanamycin A, selective inhibitors of the vacuolar ATPase proton pump, are the most powerful known inhibitors of LF macrophage toxicity. These inhibitors are fully active long after LF addition to macrophages, suggesting that LF enters the cytosol after having reached a late endosomal compartment.
Ménard
A
A
Centro CNR Biomembrane and Dipartimento di Scienze Biomediche, Università di Padova, Padua, Italy.
Altendorf
K
K
Breves
D
D
Mock
M
M
Montecucco
C
C
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D000942:Antigens, Bacterial; D001408:Bacillus anthracis; D001427:Bacterial Toxins / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000633:toxicity*; D002460:Cell Line; D003601:Cytotoxicity Tests, Immunologic; D018942:Macrolides; D008264:Macrophages / Q000166:cytology; D051379:Mice; D054328:Proton Pump Inhibitors; D017494:Proton Pumps / Q000378:metabolism*; D006180:Proton-Translocating ATPases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014617:Vacuoles
D000900:Anti-Bacterial Agents; D000942:Antigens, Bacterial; D001427:Bacterial Toxins; D018942:Macrolides; D054328:Proton Pump Inhibitors; D017494:Proton Pumps; C030325:anthrax toxin; C036978:concanamycin A; D006180:Proton-Translocating ATPases