抗真菌药物耐药性的遗传基础
Genetic Basis of Antifungal Drug Resistance.
作者信息
Marie Chelsea, White Theodore C
机构信息
Department of Medicine, University of Virginia, Charlottesville, VA, USA.
出版信息
Curr Fungal Infect Rep. 2009 Sep 1;3(3):163-169. doi: 10.1007/s12281-009-0021-y.
Abstract
Antifungal resistance caused by mutations of the drug target, overexpression of the drug target, and drug efflux by the upregulation of transporters is increasingly common. Recently our understanding of fungal drug resistance has been advanced by the identification of three key transcriptional regulators of resistance: Tac1p, Upc2p, and Mrr1p. The discovery of hyperactive variants of these regulators in resistant clinical isolates confirms the importance of transcriptional regulation in the development of antifungal resistance. Alternative mechanisms of drug resistance including aneuploidy and biofilm formation have recently been documented in fungi; as well as the phenomenon of drug tolerance. Characterization of the transcriptional regulation of fungal drug resistance and the identification of novel mechanisms of resistance has implications for current therapy and for the development of future antifungal drugs.
摘要
由药物靶点突变、药物靶点过表达以及转运蛋白上调导致的药物外排所引起的抗真菌耐药性日益普遍。最近，通过鉴定三种关键的耐药转录调节因子：Tac1p、Upc2p和Mrr1p，我们对真菌耐药性的认识有了进一步提高。在耐药临床分离株中发现这些调节因子的高活性变体，证实了转录调控在抗真菌耐药性发展中的重要性。最近在真菌中记录了包括非整倍体和生物膜形成在内的其他耐药机制；以及药物耐受性现象。真菌耐药性转录调控的特征以及新耐药机制的鉴定，对当前治疗和未来抗真菌药物的开发具有重要意义。
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