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 int erfering with the cytochrome P-450 dependent 14 alpha-demethylase. Ele ctron microscope examination revealed that a low dose (3 mu g/ml), sho rt treatment (1-3 h) with this compound greatly stimulated autophagic activity not accompanied by alterations of the cell organelles. Only r arely, 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 ergostero l and the consequent accumulation of 14 alpha-methylsterols, changes a re induced in the properties of the tonoplast. it seems that in the pr esence 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. Fluconaz ole may be useful for indicating the mechanism for controlling lytic a ctivity and the homeostatic role of the vacuole in yeasts.