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用简单荧光试验检测布氏锥虫对含砷药物的耐药性。

Detection of arsenical drug resistance in Trypanosoma brucei with a simple fluorescence test.

作者信息

Stewart Mhairi L, Krishna Sanjeev, Burchmore Richard J S, Brun Reto, de Koning Harry P, Boykin David W, Tidwell Richard R, Hall J Ed, Barrett Michael P

机构信息

University of Glasgow, Division of Infection and Immunity, Institute of Biomedical and Life Sciences, The Joseph Black Building, Glasgow G12 8QQ, UK.

出版信息

Lancet. 2005;366(9484):486-7. doi: 10.1016/S0140-6736(05)66793-1.

Abstract

The resurgence of human African trypanosomiasis (HAT), coupled with an increased incidence of drug resistance, is of concern. We report a quick, simple, and sensitive test for identification of parasites resistant to melarsoprol, the main drug used to treat late stage HAT. Resistant parasites are defective in a plasma membrane transporter responsible for drug uptake. The same transporter carries the fluorescent diamidine DB99 (2,5-bis-(4-amidinophenyl)-3,4-dimethylfuran) into trypanosomes. The two DNA-containing structures in the trypanosome--the nucleus and the kinetoplast--begin to fluoresce within 1 min of introduction of DB99, unless drug resistant.

摘要

人类非洲锥虫病(HAT)的死灰复燃,再加上耐药性发病率的上升,令人担忧。我们报告了一种快速、简单且灵敏的检测方法,用于鉴定对美拉胂醇耐药的寄生虫,美拉胂醇是治疗晚期HAT的主要药物。耐药寄生虫在负责药物摄取的质膜转运蛋白上存在缺陷。同一种转运蛋白将荧光双脒DB99(2,5-双-(4-脒基苯基)-3,4-二甲基呋喃)转运到锥虫体内。锥虫体内的两个含DNA结构——细胞核和动基体——在引入DB99后1分钟内开始发出荧光,除非是耐药的。

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