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

FEBS Letters

Loeffler, J²  Kelly, D.E¹  Kelly, S.L¹  Einsele, H²  Lamb, D.C¹  Hebart, H²  Manning, N.J³  Schumacher, U⁴ 

[1] Krebs Institute for Biomolecular Research, Department of Molecular Biology and Biotechnology, Sheffield University, Sheffield S10 2UH, UK;Medizinische Klinik, Abt. II, Eberhard-Karls Universität Tübingen, Otfried-Mueller-Str. 10, 72076 Tübingen, Germany;Neonatal Screening Laboratory, Sheffield Childrens Hospital, Western Bank, Sheffield S10 2UH, UK;Hygiene-Institut, Abt. Med. Mikrobiologie, Eberhard-Karls Universität Tübingen, Otfried-Mueller-Str. 10, 72076 Tübingen, Germany

关键词: Fluconazole;    Candidosis;    Cross-resistance;    P450 inhibition;   

DOI  :  10.1016/S0014-5793(96)01360-9

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown