The dihydrofolate reductase-thymidylate synthetase gene in the drug resistance of malaria parasites

J. E. Hyde

doi:10.1016/0163-7258(90)90017-V

The dihydrofolate reductase-thymidylate synthetase gene in the drug resistance of malaria parasites

J. E. Hyde

Research output: Contribution to journal › Article › peer-review

Abstract

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.

Original language	English
Pages (from-to)	45-59
Number of pages	14
Journal	Pharmacology and Therapeutics
Volume	48
Issue number	1
DOIs	https://doi.org/10.1016/0163-7258(90)90017-V
Publication status	Published - 1990

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abstract = "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.",

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AB - 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.

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DO - 10.1016/0163-7258(90)90017-V

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JO - Pharmacology and Therapeutics

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The dihydrofolate reductase-thymidylate synthetase gene in the drug resistance of malaria parasites

Abstract

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