Summary: Fluconazole, ketoconazole and tioconazole were shown to act synergistically with the antibiotic nikkomycin X/Z on the pathogenic fungus . The phenomenon was demonstrated using a checkerboard technique and growth inhibition experiments. The azole antifungal agents, even at concentrations not affecting growth, decreased the incorporation of the C-label from [C]glucose into chitin of the candidal cell wall. After 3 h incubation with tioconazole, 1 μg ml, the incorporation of the radiolabelled glucose into chitin of intact cells and regenerating spheroplasts of was inhibited by 43% and 30%, respectively. Moreover, the relative chitin content was approximately 45% lower than that of control cells. The chitin content increased after prolonged incubation with azoles, thus confirming the known phenomenon of azole-induced uncoordinated chitin synthesis and deposition. On the other hand, azole derivatives had very little effect on the rate of nikkomycin transport into cells. A sequential blockade mechanism of synergism is proposed.


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