Effects of fluconazole on the sterol and carbohydrate composition of four species ofCandida

Abstract

The effects of fluconazole, a bis-triazole antifungal agent, on the sterol and carbohydrate composition ofCandida albicans, Candida tropicalis, Candida krusei andCandida parapsilosis were investigated. Exposure ofCandida species to fluconazole resulted in a profound depletion of ergosterol with a corresponding increase in lanosterol content versus control cells. Carbohydrate analysis revealed a significant increase in chitin and either a decrease(Candida albicans, Candida tropicalis andCandida parapsilosis) or an increase(Candida krusei) in glucan content in fluconazole-treated cells. The decreased ergosterol and increased lanosterol content is consistnet with 14-alpha-demethylase inhibition by fluconazole. The increase in cell wall chitin is most likely due to deregulation of chitin synthesis secondary to ergosterol depletion in the cell membrane. Because chitin, glucan and ergosterol are critical components of the fungal cell, perturbation of the production and localization of these components by fluconazole is likely to contribute to the selective toxicity of this compound toCandida species and other fungi.