Effect of two imidazole antimycotics, clotrimazole and miconazole on amino acid transport inCandida albicans

Effect of the two imidazole antimycotics, clotrimazole and miconazole, on the uptake of leucine, lysine and several other amino acids by starved cells of Candida albicans was studied. Both imidazoles at concentrations around the minimum growth-inhibitory concentration substantially decreased the rate of uptake and the level in the pool of these amino acids when the cells were incubated in the absence of glucose. Inhibition by the 2 imidazoles, particularly clotrimazole, of uptake of leucine or lysine was markedly antagonized by exogenous glucose. However, such a protective effect of glucose was completely nullified when blasticidin S, a preferential inhibitor of protein synthesis, was added to the cells along with glucose. Under all of these experimental conditions, the 2 imidazoles inhibited the accumulation of leucine in the intracellular pool more profoundly than the corresponding overall incorporation of this amino acid into proteins. The imidazoles caused an efflux of previously accumulated leucine at drug concentrations comparable to those producing appreciable inhibition of leucine uptake. On the basis of its antifungal activity, miconazole appeared to be more potent in this membrane action than clotrimazole, particularly in the presence of exogenous glucose, although there was no qualitative difference between the mechanism of action of the two imidazoles.