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14α-甾醇去甲基化酶基因cyp51A中的一个点突变导致烟曲霉对伊曲康唑耐药。

A point mutation in the 14alpha-sterol demethylase gene cyp51A contributes to itraconazole resistance in Aspergillus fumigatus.

作者信息

Diaz-Guerra T M, Mellado E, Cuenca-Estrella M, Rodriguez-Tudela J L

机构信息

Unidad de Micología, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain.

出版信息

Antimicrob Agents Chemother. 2003 Mar;47(3):1120-4. doi: 10.1128/AAC.47.3.1120-1124.2003.

Abstract

The genes encoding 14alpha-sterol demethylases (cyp51A and cyp51B) were analyzed in 12 itraconazole (ITC)-resistant and three ITC-susceptible clinical isolates of Aspergillus fumigatus. Six ITC-resistant strains exhibited a substitution of another amino acid for glycine at position 54, which is located at a very conserved region of the Cyp51A protein. The cyp51A gene from the A. fumigatus wild-type strain (CM-237) was replaced with the mutated cyp51A gene copy of an ITC-resistant strain (AF-72). Two transformants exhibited resistance to ITC, both of which had incorporated the mutated copy of the cyp51A gene.

摘要

对12株耐伊曲康唑(ITC)和3株对ITC敏感的烟曲霉临床分离株进行了编码14α-甾醇脱甲基酶(cyp51A和cyp51B)的基因分析。6株耐ITC菌株在位于Cyp51A蛋白非常保守区域的第54位氨基酸处发生了甘氨酸被另一种氨基酸取代的情况。用一株耐ITC菌株(AF-72)的突变cyp51A基因拷贝替换了烟曲霉野生型菌株(CM-237)的cyp51A基因。两个转化体表现出对ITC的抗性,二者均整合了cyp51A基因的突变拷贝。

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