Biosynthesis of wall components in yeast and filamentous fungi

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.

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Effects of cilofungin (LY121019) on carbohydrate and sterol composition ofCandida albicans

Pfaller

Riley

Koerner

1989

Eur. J. Clin. Microbiol. Infect. Dis.

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Cilofungin (LY 121019) is a novel analogue of echinocandin B with potent activity against Candida albicans. The effects of cilofungin on the sterol and cell wall carbohydrate composition of Candida albicans were investigated. Exposure of Candida albicans to cilofungin resulted in a 55-60% decrease in ergosterol and a 4-13% decrease in lanosterol content relative to controls. Carbohydrate analysis revealed a 72-79% decrease in glucan content and no significant decrease in mannan or chitin content relative to controls. These studies suggest that cilofungin specifically inhibits glucan synthesis in Candida albicans and thus may be less toxic to mammalian cells. The effects of cilofungin on sterol composition may be non-specific and will require additional investigation.

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Biosynthesis of wall components in yeast and filamentous fungi

Cited by 3 publications

References 116 publications

Biochemical Targets for Antifungal Azole Derivatives: Hypothesis on the Mode of Action

Biochemical Targets for Antifungal Azole Derivatives: Hypothesis on the Mode of Action

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

Effects of cilofungin (LY121019) on carbohydrate and sterol composition ofCandida albicans

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