Analysis of pfmdr1 and drug susceptibility in fresh isolates of Plasmodium falciparum from subsaharan Africa
Analysis of pfmdr1 and drug susceptibility in fresh isolates of Plasmodium falciparum from subsaharan Africa
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DOI：
10.1016/0166-6851(95)02492-1
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发表时间：
1995-11-01
影响因子：
1.5
通讯作者：
Wilson, CM
中科院分区：
文献类型：
--
作者：
Basco, LK;LeBras, J;Wilson, CM
在大多数流行地区，恶性疟原虫对许多治疗药物的耐药性是一个日益严重的问题。恶性疟原虫的mdr样基因产物在对含喹啉化合物的耐药中的作用尚不清楚，本研究的目的是进一步研究pfmdr1在源自非洲的新鲜临床分离株耐药性中的作用，对51个新鲜临床分离株进行药敏试验（氯喹、甲氟喹、卤泛群和奎宁）并对pfmdr1进行分子分析。氯喹敏感性表型与 pfmdr1 基因内等位基因之间的统计关联在第 86 位氨基酸处被发现，该位点先前与氯喹耐药性相关。先前与氯喹耐药性相关的其他基因内等位基因几乎没有变化。pfmdr1 基因内等位基因变异与甲氟喹、卤泛群或奎宁的易感性之间没有发现相关性。在对选定分离株的分析中，pfmdr1 的基因拷贝数与任何耐药表型之间没有关联。这与其他数据一起表明，非洲和东南亚菌株中的甲氟喹耐药性可能是通过两种不同的机制产生的。本研究中注意到 pfmdr1 基因的聚天冬酰胺区域的变异性比之前报道的要大得多。此外，使用多重 PCR 的指纹分析揭示了这些分离株之间相当大的遗传变异性。
Resistance of Plasmodium falciparum to many therapeutic agents is an increasing problem in most endemic areas. The role of the mdr-like gene products of P. falciparum in resistance to quinoline-containing compounds is not clear, The purpose of this study was to further examine the role of pfmdr1 in drug resistance in fresh clinical isolates originating from Africa, Drug susceptibility testing (chloroquine, mefloquine, halofantrine and quinine) and a molecular analysis of pfmdr1 was completed for 51 fresh clinical isolates. A statistical association between the chloroquine sensitivity phenotype and an intragenic allele of pfmdr1 was noted at a position, amino acid 86, which was previously associated with chloroquine resistance, There was little variation in the other intragenic alleles previously associated with chloroquine resistance, No correlation between pfmdr1 intragenic allelic variation and susceptibility to mefloquine, halofantrine or quinine was found. There was no association between gene copy number of pfmdr1 and any drug resistant phenotype in an analysis of selected isolates. This, along with other data, suggests that mefloquine resistance may have arisen by two different mechanisms in African and Southeast Asian isolates. Much more variability in the polyasparaginated region of the pfmdr1 gene was noted in this study than previously reported. In addition, fingerprint analysis using multiplex PCR revealed considerable genetic variability among these isolates.