Effects of terconazole and other azole antifungal agents on the sterol and carbohydrate composition of Candida albicans.
The effects of terconazole, a triazole antifungal, on the sterol and carbohydrate composition of Candida albicans was compared with that of three imidazoles: clotrimazole, miconazole, and butoconazole. Exposure of C. albicans to terconazole resulted in a profound depletion of ergosterol with a corresponding increase in lanosterol content versus control cells. Carbohydrate analysis revealed a significant (245%) increase in chitin and a minimal effect on glucan and mannan in terconazole-treated cells. Similar effects on sterol and carbohydrate composition were observed with clotrimazole and miconazole. Butoconazole had a similar effect on sterol composition but had no effect on carbohydrate composition. The decreased ergosterol and increased lanosterol content is consistent with 14 alpha-demethylase inhibition by terconazole and the other azoles. The increase in cell wall chitin is most likely due to deregulation of chitin synthesis secondary to ergosterol depletion in the cell membrane. Because both chitin and ergosterol are critical components of the fungal cell, perturbation of the production and localization of these components by terconazole is likely to contribute to the selective toxicity of this compound for C. albicans and other fungi.
Veterans Administration Medical Center, Iowa City, Iowa.
M A
MA
Pfaller
J
J
Riley
T
T
Koerner
D000935:Antifungal Agents / Q000494:pharmacology*; D002176:Candida albicans / Q000032:analysis / Q000187:drug effects*; D002241:Carbohydrates / Q000032:analysis*; D002458:Cell Fractionation; D002473:Cell Wall / Q000032:analysis; D002686:Chitin / Q000032:analysis; D003022:Clotrimazole / Q000494:pharmacology; D004875:Ergosterol / Q000032:analysis; D005936:Glucans / Q000032:analysis; D007093:Imidazoles / Q000494:pharmacology; D007810:Lanosterol / Q000032:analysis; D008351:Mannans / Q000032:analysis; D008825:Miconazole / Q000494:pharmacology; D013261:Sterols / Q000032:analysis*; D014230:Triazoles / Q000494:pharmacology*
D000935:Antifungal Agents; D002241:Carbohydrates; D005936:Glucans; D007093:Imidazoles; D008351:Mannans; D013261:Sterols; D014230:Triazoles; C037815:terconazole; C017125:butoconazole; D002686:Chitin; D007810:Lanosterol; D008825:Miconazole; D003022:Clotrimazole; D004875:Ergosterol