Volkman S K, Cowman A F, Wirth D F
Department of Tropical Public Health, Harvard School of Public Health, Boston, MA 02115, USA.
Proc Natl Acad Sci U S A. 1995 Sep 12;92(19):8921-5. doi: 10.1073/pnas.92.19.8921.
The pfmdr1 gene has been associated with a drug-resistant phenotype in Plasmodium falciparum, and overexpression of pfmdr1 has been associated with mefloquine- and halofantrine-resistant parasites, but little is known about the functional role of pfmdr1 in this process. Here, we demonstrate that the pfmdr1 gene expressed in a heterologous yeast system functions as a transport molecule and complements a mutation in ste6, a gene which encodes a mating pheromone a-factor export molecule. In addition, the pfmdr1 gene containing two mutations which are associated with naturally occurring chloroquine resistance abolishes this mating phenotype, suggesting that these genetic polymorphisms alter this transport function. Our results support the functional role of pfmdr1 as a transport molecule in the mediation of drug resistance and provide an assay system to address the nature of this transport function.
pfmdr1基因已与恶性疟原虫的耐药表型相关联，pfmdr1的过表达已与对甲氟喹和卤泛群耐药的寄生虫相关，但关于pfmdr1在此过程中的功能作用知之甚少。在此，我们证明在异源酵母系统中表达的pfmdr1基因作为一种转运分子发挥作用，并弥补了ste6基因（该基因编码一种交配信息素a因子输出分子）中的突变。此外，含有两个与天然存在的氯喹抗性相关的突变的pfmdr1基因消除了这种交配表型，表明这些基因多态性改变了这种转运功能。我们的结果支持pfmdr1作为转运分子在介导耐药性中的功能作用，并提供了一个分析系统来研究这种转运功能的本质。
