Hyde J E
Department of Biochemistry and Applied Molecular Biology, University of Manchester Institute of Science and Technology (UMIST), U.K.
Pharmacol Ther. 1990;48(1):45-59. doi: 10.1016/0163-7258(90)90017-v.
Resistance to antifolate drugs such as pyrimethamine is widespread among malaria parasites of the most pathogenic species Plasmodium falciparum. These drugs inhibit the dihydrofolate reductase activity of the dihydrofolate reductase-thymidylate synthetase (DHFR-TS) bifunctional enzyme. This review examines work done to characterize the enzyme, the cloning of plasmodial DHFR-TS genes, chromosomal mapping studies of these genes by pulsed-field gel electrophoresis, and the structural insights into the mechanism of drug resistance that have been gained by comparing genes from drug-sensitive parasites with those from drug-resistant strains that have arisen in the field or after experimental induction.
对乙胺嘧啶等抗叶酸药物的耐药性在最具致病性的疟原虫物种恶性疟原虫的疟原虫中广泛存在。这些药物抑制二氢叶酸还原酶-胸苷酸合成酶（DHFR-TS）双功能酶的二氢叶酸还原酶活性。本综述考察了为鉴定该酶所做的工作、疟原虫DHFR-TS基因的克隆、通过脉冲场凝胶电泳对这些基因进行的染色体定位研究，以及通过比较来自药物敏感寄生虫的基因与来自在野外或实验诱导后出现的耐药菌株的基因所获得的关于耐药机制的结构见解。
