Melarsoprol- and pentamidine-resistant Trypanosoma brucei rhodesiense populations and their cross-resistance
Melarsoprol- and pentamidine-resistant Trypanosoma brucei rhodesiense populations and their cross-resistance
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DOI：
10.1016/j.ijpara.2007.05.007
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发表时间：
2007-11-01
影响因子：
4
通讯作者：
Brun, Reto
中科院分区：
文献类型：
--
作者：
Bernhard, Sonja C.;Nerima, Barbara;Brun, Reto
体外诱导血流型布氏锥虫STIB 900对美拉胂醇和喷他脒产生耐药性，并测定其对美拉胂醇、喷他脒和呋喃脒的药物敏感性。还将耐药群体接种到免疫抑制小鼠中以验证感染性并监测啮齿动物传代是否选择具有改变的药物敏感性的克隆。在小鼠中增殖后，分离锥虫并测定它们对三种药物的IC 50值。为了评估药物诱导的耐药性的稳定性，停止药物压力2个月，并再次测定药物敏感性。耐药性是稳定的，有几个例外，讨论。药物IC（50）表明所有药物之间存在交叉耐药性，但程度不同：美拉胂醇选择性和戊烷脒选择性锥虫对戊烷脒的耐药性相同，但戊烷脒选择性锥虫群体对美拉胂醇的耐药性低于美拉胂醇选择性锥虫。有趣的是，这两个耐药群体显示出相同的中间交叉耐药性呋喃脒。耐药锥虫种群的特点是分子手段，指的是TbAT1基因的状态。美拉胂醇选择的种群显然已经失去了TbAT 1，而在喷他脒选择的锥虫种群中，它仍然存在。(c)2007年澳大利亚寄生虫学会由爱思唯尔有限公司出版。保留所有权利。
Resistance to melarsoprol and pentamidine was induced in bloodstream-form Trypanosoma brucei rhodesiense STIB 900 in vitro, and drug sensitivity was determined for melarsoprol, pentamidine and furamidine. The resistant populations were also inoculated into immunosuppressed mice to verify infectivity and to monitor whether rodent passage selects for clones with altered drug sensitivity. After proliferation in the mouse, trypanosomes were isolated and their IC50 values to the three drugs were determined. To assess the stability of drug-induced resistance, drug pressure was ceased for 2 months and the drug sensitivity was determined again. Resistance was stable, with a few exceptions that are discussed. Drug IC(50)s indicated cross-resistance among all drugs, but to varying extents: resistance of the melarsoprol-selected and pentamidine-selected trypanosomes to pentamidine was the same, but the pentamidine-selected trypanosome population showed lower resistance to melarsoprol than the melarsoprol-selected trypanosomes. Interestingly, both resistant populations revealed the same intermediate cross-resistance to furamidine. Resistant trypanosome populations were characterised by molecular means, referring to the status of the TbAT1 gene. The melarsoprol-selected population apparently had lost TbAT1, whereas in the pentamidine-selected trypanosome population it was still present. (c) 2007 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.