MODE OF ACTION AND RESISTANCE TO AZOLE ANTIFUNGALS ASSOCIATED WITH THE FORMATION OF 14-ALPHA-METHYLERGOSTA-8,24(28)-DIEN-3-BETA,6-ALPHA-DIOL

被引：236

作者：

KELLY, SL ^{[1
]}

LAMB, DC ^{[1
]}

CORRAN, AJ ^{[1
]}

BALDWIN, BC ^{[1
]}

KELLY, DE ^{[1
]}

机构：

[1] ZENECA AGROCHEM,JEALOTTS HILL RES STN,BRACKNELL RG12 6EY,BERKS,ENGLAND

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 1995年 / 207卷 / 03期

关键词：

D O I：

10.1006/bbrc.1995.1272

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 antifungal compounds inhibit sterol 14 alpha-demethylase. They are used extensively for the treatment of immunocompromised patients where fungal infection is common and often results in death. Resistance to the compounds is emerging, particularly in fungal pathogens obtained from AIDS patients undergoing prolonged therapy. We show here that cell growth arrest correlates with the accumulation of 14 alpha-methyl-ergosta-8,24(28)-dien-3 beta,6 alpha-diol in a yeast strain with a sterol 14 alpha-demethylase gene disruption, which mimics stringent treatment conditions. Cells can overcome the effect of such a block by a suppressor mutation in sterol Delta(5,6) desaturation and acquire azole resistance. Plasmid-based complementation of the sterol 14 alpha-demethylase defect does not alter the azole susceptibility of strains containing these suppressor mutations, showing resistance is due entirely to the Delta(5,6) desaturase defect. (C) 1995 Academic Press, Inc.

引用

页码：910 / 915

页数：6