Premium
Resistance to fluconazole and cross‐resistance to amphotericin B in Candida albicans from AIDS patients caused by defective sterol Δ 5,6 ‐desaturation
Author(s) -
Kelly S.L,
Lamb D.C,
Kelly D.E,
Manning N.J,
Loeffler J,
Hebart H,
Schumacher U,
Einsele H
Publication year - 1997
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(96)01360-9
Subject(s) - fluconazole , sterol , amphotericin b , ergosterol , candida albicans , microbiology and biotechnology , cross resistance , biology , azole , drug resistance , antifungal , corpus albicans , mycosis , pharmacology , immunology , biochemistry , cholesterol
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 Δ 5,6 ‐desaturation. This altered the type of sterol accumulating under fluconazole treatment from 14α‐methylergosta‐8,24(28)‐dien‐3β,6α‐diol to 14α‐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 14α‐methylergosta‐8,24(28)‐dien‐3β,6α‐diol accumulation.