Resistance to fluconazole and cross-resistance to amphotericin B in Candida albicans from AIDS patients caused by defective sterol Δ5,6 -desaturation

Abstract

Fluconazole resistance occurs in > 10% of cases of candidosis during the late stages of AIDS. We show here in two clinical isolates that resistance was caused by defective sterol delta5,6-desaturation. This altered the type of sterol accumulating under fluconazole treatment from 14alpha-methylergosta-8,24(28)-dien-3beta,6alpha -diol to 14alpha-methylfecosterol which is capable of supporting growth. A consequence of this mechanism of azole resistance is that an absence of ergosterol causes cross-resistance to the other major antifungal agent available, amphotericin B. The results also show that growth arrest after fluconazole treatment of C. albicans in clinical conditions is caused by 14alpha-methylergosta-8,24(28)-dien-3beta,6alpha -diol accumulation.