Chloroquine resistance in Plasmodium chabaudi:: are chloroquine-resistance transporter (crt) and multi-drug resistance (mdr1) orthologues involved?
Chloroquine resistance in Plasmodium chabaudi:: are chloroquine-resistance transporter (crt) and multi-drug resistance (mdr1) orthologues involved?
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DOI：
10.1016/j.molbiopara.2003.08.010
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发表时间：
2004-01-01
影响因子：
1.5
通讯作者：
Walliker, D
中科院分区：
文献类型：
--
作者：
Hunt, P;Cravo, PVL;Walliker, D
我们已经在啮齿动物疟原虫中发现了两个恶性疟原虫基因pfcrt和pfmdr1的同源物，这两个基因被认为是后者对氯喹耐药的决定因素。在氯喹敏感克隆AS中首次确定了chabaudi基因的序列，分别为pcg10和pcmdr1，与恶性疟原虫的序列高度相似。pcg10在预测编码区内的核苷酸序列同源性为68.6%，氨基酸序列同源性为75.1%。pcmdr1序列同源性分别为75.0%（核苷酸）和78.1%（氨基酸）。对3个对氯喹具有3种不同程度抗性的克隆进行了基因序列测定。所有突变体中这两个基因的序列都与产生它们的敏感AS的基因序列相同。在AS克隆和一个遗传无关的敏感克隆AJ之间发现了两个基因的多态性位点。AJ与耐药AS克隆间的遗传杂交分析显示，遗传亲本pccrt和pcmdr1等位基因与克隆后代的药物反应没有关联。这表明这两个基因及其密切相关的基因都不是chabaudi突变体对氯喹抗性的决定因素。(C) 2003 Elsevier B.V.版权所有
We have identified in the rodent malaria parasite Plasmodium chabaudi orthologues of two Plasmodium falciparum genes, pfcrt and pfmdr1 which have been implicated as determinants of chloroquine resistance in the latter species. The sequences of the R chabaudi genes, denoted, respectively, pccg10 and pcmdr1, were first determined in the chloroquine-sensitive clone AS, and found to be highly similar to those of P. falciparum. For pccg10, there was a nucleotide sequence identity of 68.6% and amino acid sequence identity of 75.1% within the predicted coding region. For pcmdr1, the sequence identities were 75.0% (nucleotide) and 78.1% (amino acid). The sequences of the genes were then determined in three P. chabaudi clones selected from clone AS which possessed three different levels of resistance to chloroquine. The sequences of both genes in all mutants were found to be identical to those of the sensitive AS from which they had been derived. Polymorphic sites were found in both genes between the AS clones and a genetically unrelated sensitive clone AJ. Analysis of genetic crosses between AJ and resistant AS clones showed no linkage between inherited parental alleles of pccrt and pcmdr1 and drug responses of the cloned progeny. This showed that neither of these genes, nor genes closely linked to them, were determinants of the chloroquine resistance in the P. chabaudi mutants. (C) 2003 Elsevier B.V. All rights reserved.