Stimulation of the autophagic activity in blastospores of Candida albicans exposed in vitro to fluconazole.

Blastospores of Candida albicans were exposed in vitro to fluconazole, a bis-triazole which inhibits ergosterol biosynthesis in fungi by interfering with the cytochrome P-450 dependent 14 alpha-demethylase. Electron microscope examination revealed that a low dose (3 micrograms/ml), short treatment (1-3 h) with this compound greatly stimulated autophagic activity not accompanied by alterations of the cell organelles. Only rarely, wall thickenings and some damage to the membrane system, except for the plasma membrane, was noted. This unusual phenomenon suggests that in the presence of fluconazole, due to the depletion of ergosterol and the consequent accumulation of 14 alpha-methylsterols, changes are induced in the properties of the tonoplast. It seems that in the presence of the molecule the membrane is not able to distinguish what is to be degraded from what is still useful for intracellular metabolism with the consequent disintegration of cell compartmentation. Fluconazole may be useful for indicating the mechanism for controlling lytic activity and the homeostatic role of the vacuole in yeasts.