Resistance to fluconazole and cross-resistance to amphotericin B in Candida albicans from AIDS patients caused by defective sterol Delta(5,6)-desaturation

被引：266

作者：

Kelly, SL

Lamb, DC

Kelly, DE

Manning, NJ

Loeffler, J

Hebart, H

Schumacher, U

Einsele, H

机构：

[1] SHEFFIELD CHILDRENS HOSP,NEONATAL SCREENING LAB,WESTERN BANK,SHEFFIELD S10 2UH,S YORKSHIRE,ENGLAND

[2] UNIV TUBINGEN,MED CLIN,ABT 2,D-72076 TUBINGEN,GERMANY

[3] UNIV TUBINGEN,INST HYG,ABT MED MIKROBIOL,D-72076 TUBINGEN,GERMANY

来源：

FEBS LETTERS | 1997年 / 400卷 / 01期

关键词：

fluconazole; candidosis; cross-resistance; P450; inhibition;

D O I：

10.1016/S0014-5793(96)01360-9

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

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 Delta(5),(6)-desaturation. This altered the type of sterol accumulating under fluconazole treatment from 14 alpha-methylergosta-8,24(28)-dien-3 beta,6 alpha-diol to 14 alpha-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 14 alpha(methylergosta-8,24(28)-dien-3 beta,6 alpha-diol accumulation.

引用

页码：80 / 82

页数：3

共 9 条

[1] FLUCONAZOLE-RESISTANT CANDIDOSIS IN AN HIV COHORT [J].