Genetic analysis of the dihydrofolate reductase-thymidylate synthase gene from geographically diverse isolates of Plasmodium malariae

Naowarat Tanomsing, Mallika Imwong, Sasithon Pukrittayakamee, Kesinee Chotivanich, Sornchai Looareesuwan, Mayfong Mayxay, Christiane Dolecek, Tinh Hien Tran, Virgilio Estólio do Rosário, Ana Paula Arez, Pascal Michon, Georges Snounou, Nicholas J. White, Nicholas P J Day

Research output: Contribution to journalArticlepeer-review

18 Citations (Scopus)

Abstract

Plasmodium malariae, the parasite responsible for quartan malaria, is transmitted in most areas of malaria endemicity and is associated with significant morbidity. The sequence of the gene coding for the enzyme dihydrofolate reductase-thymidylate synthase (DHFR-TS) was obtained from field isolates of P. malariae and from the closely related simian parasite Plasmodium brasilianum. The two sequences were nearly 100% homologous, adding weight to the notion that they represent genetically distinct lines of the same species. A survey of polymorphisms of the dhfr sequences in 35 isolates of P. malariae collected from five countries in Asia and Africa revealed a low number of nonsynonymous mutations in five codons. In five of the isolates collected from southeast Asia, a nonsynonymous mutation was found at one of the three positions known to be associated with antifolate resistance in other Plasmodium species. Five isolates with the wild-type DHFR could be assayed for drug susceptibility in vitro and were found to be sensitive to pyrimethamine (mean 50% inhibitory concentration, 2.24 ng/ml [95% confidence interval, 0.4 to 3.1]).

Original languageEnglish
Pages (from-to)3523-3530
Number of pages8
JournalAntimicrobial Agents and Chemotherapy -Journal-
Volume51
Issue number10
DOIs
Publication statusPublished - Oct 2007

Fingerprint

Dive into the research topics of 'Genetic analysis of the dihydrofolate reductase-thymidylate synthase gene from geographically diverse isolates of Plasmodium malariae'. Together they form a unique fingerprint.

Cite this