Wilson C M, Volkman S K, Thaithong S, Martin R K, Kyle D E, Milhous W K, Wirth D F
Department of Tropical Public Health, Harvard School of Public Health, Boston, MA 02115.
Mol Biochem Parasitol. 1993 Jan;57(1):151-60. doi: 10.1016/0166-6851(93)90252-s.
Drug resistance in Plasmodium falciparum is an expanding problem in most endemic areas. Recent studies have suggested the potential involvement of genes in the MDR gene family in resistance to quinoline-containing compounds in P. falciparum. In this study a molecular analysis of pfmdr 1 in recent isolates from Thailand was done (1) to further examine the role of pfmdr 1 in drug-resistant isolates and (2) to examine the reported association of pfmdr 1 intragenic alleles and chloroquine resistance. Most of the isolates (10 of 11) were resistant to all compounds tested. Analysis of pfmdr 1 revealed an apparent association between increased gene copy number and increased level of expression of pfmdr 1 and decreased susceptibility to mefloquine and halofantrine. Sequence analysis of pfmdr 1 in these isolates revealed no association of intragenic alleles with chloroquine resistance.
恶性疟原虫的耐药性在大多数流行地区是一个不断扩大的问题。最近的研究表明,多药耐药(MDR)基因家族中的基因可能参与了恶性疟原虫对含喹啉化合物的耐药性。在本研究中,对来自泰国的近期分离株进行了pfmdr 1的分子分析,(1)以进一步研究pfmdr 1在耐药分离株中的作用,(2)研究报道的pfmdr 1基因内等位基因与氯喹耐药性之间的关联。大多数分离株(11株中的10株)对所有测试化合物耐药。pfmdr 1分析显示,基因拷贝数增加与pfmdr 1表达水平升高以及对甲氟喹和卤泛群敏感性降低之间存在明显关联。对这些分离株中pfmdr 1的序列分析显示,基因内等位基因与氯喹耐药性无关联。