ALTERED P450 ACTIVITY ASSOCIATED WITH DIRECT SELECTION FOR FUNGAL AZOLE RESISTANCE

被引：49

作者：

JOSEPHHORNE, T ^{[1
]}

HOLLOMON, D ^{[1
]}

LOEFFLER, RST ^{[1
]}

KELLY, SL ^{[1
]}

机构：

[1] UNIV BRISTOL,INST ARABLE CROPS RES,DEPT AGR SCI,LONG ASHTON RES STN,BRISTOL BS18 GAF,AVON,ENGLAND

来源：

FEBS LETTERS | 1995年 / 374卷 / 02期

基金：

英国生物技术与生命科学研究理事会;

关键词：

CYTOCHROME P450; AZOLE; RESISTANCE;

D O I：

10.1016/0014-5793(95)01102-K

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：

Azole antifungals inhibit CYP51A1-mediated sterol 14 alpha-demethylation and the mechanism(s) of resistance to such compounds in Ustilago maydis were examined, The inhibition of growth was correlated with the accumulation of the substrate, 24-methylene-24,25-dihydrolanosterol (eburicol), and depletion of ergosterol, Mutants overcoming the effect of azole antifungal treatment exhibited a unique phenotype with leaky CYP51A1. activity which was resistant to inhibition, The results demonstrate that alterations at the level of inhibitor binding to the target site can produce azole resistance, Similar changes may account for fungal azole resistance phenomena in agriculture, and also in medicine where resistance has become a problem in immunocompromised patients suffering from AIDS.

引用

页码：174 / 178

页数：5

共 26 条

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