烟曲霉14α-甾醇去甲基化酶（Cyp51A）中第220位甲硫氨酸的替换导致其在体外对唑类抗真菌药物产生耐药性。
Substitutions at methionine 220 in the 14alpha-sterol demethylase (Cyp51A) of Aspergillus fumigatus are responsible for resistance in vitro to azole antifungal drugs.
作者信息
Mellado E, Garcia-Effron G, Alcazar-Fuoli L, Cuenca-Estrella M, Rodriguez-Tudela J L
机构信息
Servicio de Micología, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Carretera Majadahonda-Pozuelo Km2, 28220 Madrid, Spain.
出版信息
Antimicrob Agents Chemother. 2004 Jul;48(7):2747-50. doi: 10.1128/AAC.48.7.2747-2750.2004.
Abstract
Five clinical isolates of Aspergillus fumigatus that exhibited similar patterns of reduced susceptibility to itraconazole and other triazole drugs were analyzed. Sequence analysis of genes (cyp51A and cyp51B) encoding the 14alpha-sterol demethylases revealed that all five strains harbored mutations in cyp51A resulting in the replacement of methionine at residue 220 by valine, lysine, or threonine. When the mutated cyp51A genes were introduced into an A. fumigatus wild-type strain, the transformants exhibited reduced susceptibility to all triazole agents, confirming that the mutations were responsible for the resistance phenotype.
摘要
对五株烟曲霉临床分离株进行了分析，这些分离株对伊曲康唑和其他三唑类药物表现出相似的敏感性降低模式。对编码14α-甾醇去甲基酶的基因（cyp51A和cyp51B）进行序列分析，结果显示所有五株菌株的cyp51A均发生了突变，导致第220位残基的甲硫氨酸被缬氨酸、赖氨酸或苏氨酸取代。当将突变的cyp51A基因导入烟曲霉野生型菌株时，转化子对所有三唑类药物的敏感性均降低，证实这些突变是耐药表型的原因。
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