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

被引:47
作者
Stewart, ML
Krishna, S
Burchmore, RJS
Brun, R
de Koning, HP
Boykin, DW
Tidwell, RR
Hall, JE
Barrett, MP
机构
[1] Univ London St Georges Hosp, Sch Med, Dept Cellular & Mol Med Infect Dis, London SW17 0RE, England
[2] Georgia State Univ, Dept Chem, Atlanta, GA 30303 USA
[3] Univ N Carolina, Sch Pharm, Div Med Chem & Nat Prod, Chapel Hill, NC 27599 USA
[4] Univ N Carolina, Dept Pathol & Lab Med, Chapel Hill, NC USA
[5] Swiss Trop Inst, CH-4002 Basel, Switzerland
基金
英国惠康基金;
关键词
D O I
10.1016/S0140-6736(05)66793-1
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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.
引用
收藏
页码:486 / 487
页数:2
相关论文
共 5 条
[1]   The trypanosomiases [J].
Barrett, MP ;
Burchmore, RJS ;
Stich, A ;
Lazzari, JO ;
Frasch, AC ;
Cazzulo, JJ ;
Krishna, S .
LANCET, 2003, 362 (9394) :1469-1480
[2]   The phenomenon of treatment failures in Human African Trypanosomiasis [J].
Brun, R ;
Schumacher, R ;
Schmid, C ;
Kunz, C ;
Burri, C .
TROPICAL MEDICINE & INTERNATIONAL HEALTH, 2001, 6 (11) :906-914
[3]   ARSENICAL-RESISTANT TRYPANOSOMES LACK AN UNUSUAL ADENOSINE TRANSPORTER [J].
CARTER, NS ;
FAIRLAMB, AH .
NATURE, 1993, 361 (6408) :173-176
[4]   Mechanisms of arsenical and diamidine uptake and resistance in Trypanosoma brucei [J].
Matovu, E ;
Stewart, ML ;
Geiser, F ;
Brun, R ;
Mäser, P ;
Wallace, LJM ;
Burchmore, RJ ;
Enyaru, JCK ;
Barrett, MP ;
Kaminsky, R ;
Seebeck, T ;
de Koning, HP .
EUKARYOTIC CELL, 2003, 2 (05) :1003-1008
[5]   Characterisation of cloned lines of Trypanosoma brucei expressing stable resistance to MelCy and suramin [J].
Scott, AG ;
Tait, A ;
Turner, CMR .
ACTA TROPICA, 1996, 60 (04) :251-262