伊曲康唑
烟曲霉
流出
ATP结合盒运输机
生物
曲菌病
微生物学
基因
抗药性
运输机
曲霉
多重耐药
白色念珠菌
最小抑制浓度
抗生素
生物化学
免疫学
抗真菌
作者
John W Slaven,Michael J. Anderson,Dominique Sanglard,Graham K. Dixon,Jacques Billé,Ian S. Roberts,David W. Denning
标识
DOI:10.1016/s1087-1845(02)00016-6
摘要
Aspergillus fumigatus is the most frequent causative agent of invasive aspergillosis. Itraconazole became available in 1990 to treat invasive aspergillosis, but instances of resistance have now been described. Drug efflux was a proposed mechanism in one itraconazole resistant clinical isolate (AF72) which accumulates low levels of the drug. Drug efflux in fungi can be mediated by ATP-binding cassette transporter (ABCT) genes, such as CDR1 in Candida albicans. Using a probe derived from CDR1, a gene, atrF, was cloned from A. fumigatus. The atrF gene product (AtrF) is 1547 amino acids long and has characteristic multidrug resistance motifs. Dot blot analysis revealed that AF72 has approximately 5-fold higher levels of atrF mRNA than susceptible isolates AF10 and H06-03 in cultures with sub-minimum inhibitory concentration (sub-MIC) levels of itraconazole. atrF is the first ABCT gene cloned from A. fumigatus, whose overexpression is correlated with itraconazole resistance.
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