A protein of the leucine-rich repeats (LRRs) superfamily is implicated in antimony resistance in Leishmania infantum amastigotes
A protein of the leucine-rich repeats (LRRs) superfamily is implicated in antimony resistance in Leishmania infantum amastigotes
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DOI：
10.1016/j.molbiopara.2007.11.008
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发表时间：
2008-03-01
影响因子：
1.5
通讯作者：
Ouellette, Marc
中科院分区：
文献类型：
--
作者：
Genest, Paul-Andre;Haimeur, Anass;Ouellette, Marc
含五价锑的药物(SBV)是控制原虫寄生虫利什曼原虫的主要药物，但在一些流行地区，对这类药物的耐药性现在很普遍。在这里，我们描述了功能克隆的应用，其中来自婴儿利什曼原虫的表达粘粒库被导入婴儿利什曼原虫无性无鞭毛体中，并对酒石酸锑(SbIII)进行抗性筛选。这一策略使我们能够分离到编码一种新的抗性蛋白LinJ34.0570的粘粒，该蛋白属于富亮氨酸重复序列(LRR)超家族。过量表达这种LRR蛋白的寄生虫是LRR-CC亚家族的一部分，作为无鞭毛体对SbIII产生抗性，作为细胞内寄生虫对SBV产生抗性。这项工作发现了一种新的蛋白质，它可能有助于利什曼原虫对锑的抵抗。(C)2007 Elsevier B.V.保留所有权利。
Pentavalent antimonial containing drugs (SbV) are the mainstay for the control of the protozoan parasite Leishmania but resistance to this class of drug is now prevalent in several endemic areas. We describe here the use of functional cloning where an expression cosmid bank derived from Leishmania infantum was transfected in L. infantum axenic amastigotes and selected for potassium antimonyl tartrate (SbIII) resistance. This strategy allowed the isolation of a cosmid encoding for a novel resistance protein, LinJ34.0570, which belongs to the superfamily of leucine-rich repeat (LRR) proteins. Parasites overexpressing this LRR protein, which is part of the LRR-CC subfamily, were resistant to SbIII as axenic amastigotes and to SbV as intracellular parasites. This work pinpoints a novel protein that can contribute to antimonial resistance in Leishmania. (c) 2007 Elsevier B.V. All rights reserved.