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Title: Genetic analysis of the dihydrofolate reductase-thymidylate synthase gene from geographically diverse isolates of Plasmodium malariae
Authors: Naowarat Tanomsing
Mallika Imwong
Sasithon Pukrittayakamee
Kesinee Chotivanich
Sornchai Looareesuwan
Mayfong Mayxay
Christiane Dolecek
Tinh Hien Tran
Virgilio E. Do Rosario
Ana Paula Arez
Pascal Michon
Georges Snounou
Nicholas J. White
Nicholas P.J. Day
Mahidol University
Wellcome Trust
Universidade Nova de Lisboa, Instituto de Higiene e Medicina Tropical
Papua New Guinea Institute of Medical Research
Museum National d'Histoire Naturelle
Nuffield Department of Clinical Medicine
Keywords: Medicine;Pharmacology, Toxicology and Pharmaceutics
Issue Date: 1-Oct-2007
Citation: Antimicrobial Agents and Chemotherapy. Vol.51, No.10 (2007), 3523-3530
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]). Copyright © 2007, American Society for Microbiology. All Rights Reserved.
ISSN: 00664804
Appears in Collections:Scopus 2006-2010

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