Effects of fluconazole on the sterol and carbohydrate composition of four species of Candida.
The effects of fluconazole, a bis-triazole antifungal agent, on the sterol and carbohydrate composition of Candida albicans, Candida tropicalis, Candida krusei and Candida parapsilosis were investigated. Exposure of Candida 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 and Candida parapsilosis) or an increase (Candida krusei) in glucan content in fluconazole-treated cells. The decreased ergosterol and increased lanosterol content is consistent 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 to Candida species and other fungi.
Pfaller
M
M
Veterans Affairs Medical Center, Iowa City, Iowa.
Riley
J
J
D002175:Candida / Q000737:chemistry / Q000187:drug effects*; D002176:Candida albicans / Q000737:chemistry / Q000187:drug effects; D002241:Carbohydrates / Q000032:analysis*; D002473:Cell Wall / Q000737:chemistry / Q000187:drug effects; D002686:Chitin / Q000032:analysis; D004875:Ergosterol / Q000032:analysis; D015725:Fluconazole / Q000494:pharmacology*; D005936:Glucans / Q000032:analysis; D007810:Lanosterol / Q000032:analysis; D008351:Mannans / Q000032:analysis; D013261:Sterols / Q000032:analysis*
D002241:Carbohydrates; D005936:Glucans; D008351:Mannans; D013261:Sterols; D002686:Chitin; D007810:Lanosterol; D015725:Fluconazole; D004875:Ergosterol