Abrogation by glucose of the ATP suppression induced by miconazole in Candida albicans

Miconazole at 10 mg/l effected rapid (less than 1 min) and substantial (greater than 99%) reductions of intracellular ATP concentrations in buffered suspensions of Candida albicans. This ATP-suppressive effect was mirrored by a rapid reduction in the viable counts of the suspensions. However, the presence of exogenous glucose or fructose (but not several other carbon sources) greatly retarded the ATP-suppressive effect of miconazole. Glucose and fructose could even reverse the suppression when they were added to miconazole-pretreated suspensions. These data indicated that the non-viable cells remained metabolically active. The abrogatory effect of glucose on ATP reduction was optimal between pH 6.5 and 7: it was prevented by fluoride, a known inhibitor of glycolysis, and 2-deoxy-D-glucose could not substitute for glucose, demonstrating that metabolism of glucose was essential for the effect. Two detergents and orthovanadate were much less potent ATP suppressors than miconazole, but the proton pump uncoupler, carbonyl cyanide-p-trifluoromethoxyphenylhydrazone (FCCP) was 10 times more active. The results suggest that miconazole may reduce ATP either by uncoupling substrate uptake mechanisms dependent on the fungal membrane proton pump or by inhibition of plasma membrane ATPase.