Mäser Pascal, Lüscher Alexandra, Kaminsky Ronald
Institute of Cell Biology, University of Bern, Bern, Switzerland.
Drug Resist Updat. 2003 Oct;6(5):281-90. doi: 10.1016/j.drup.2003.09.001.
Drug resistance in African trypanosomes has been studied for almost a hundred years. Beginning with Paul Ehrlich's work that led to the chemoreceptor hypothesis, reduction of net drug uptake has emerged as the most frequent cause of resistance. This review, therefore, focuses on trypanosomal drug transporter genes. TbAT1 encodes purine permease P2, which mediates influx of melarsoprol and diamidines. Disruption of TbAT1 in Trypanosoma brucei reduced sensitivity to these trypanocides. TbMRPA encodes a putative trypanothione-conjugate efflux pump, and overexpression of TbMRPA in T. brucei causes melarsoprol resistance. It will be important to determine the role of TbAT1 and TbMRPA in sleeping sickness treatment failures.
非洲锥虫的耐药性已被研究了近百年。从保罗·埃利希的工作引出化学感受器假说开始，药物净摄取减少已成为最常见的耐药原因。因此，本综述聚焦于锥虫药物转运蛋白基因。TbAT1编码嘌呤通透酶P2，它介导美拉胂醇和双脒的流入。布氏锥虫中TbAT1的缺失降低了对这些锥虫杀灭剂的敏感性。TbMRPA编码一种假定的锥虫硫醇共轭物外排泵，布氏锥虫中TbMRPA的过表达导致美拉胂醇耐药。确定TbAT1和TbMRPA在昏睡病治疗失败中的作用将很重要。
