Journal
INTERNATIONAL JOURNAL FOR PARASITOLOGY
Volume 41, Issue 2, Pages 165-171Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.ijpara.2010.08.008
Keywords
Plasmodium; Sulphadoxine; Folate; Mutation; mdr2
Categories
Funding
- Fundacao para a Ciencia e a Tecnologia (FCT) of Portugal [SFRH/BPD/35017/2007, SFRH/BD/63129/2009]
- Wellcome Trust Centre-in-Development in Immunity, Infection and Evolution (UK) [082611/Z/07/Z]
- Medical Research Council, UK [G0400476]
- FCT [PTDC/SAU-MII/65028/2006]
- Fundação para a Ciência e a Tecnologia [SFRH/BPD/35017/2007, SFRH/BD/63129/2009, PTDC/SAU-MII/65028/2006] Funding Source: FCT
- MRC [G0400476] Funding Source: UKRI
- Wellcome Trust [082611/Z/07/Z] Funding Source: Wellcome Trust
- Medical Research Council [G0400476] Funding Source: researchfish
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In malaria parasites, mutations in two genes of folate biosynthesis encoding dihydrofolate reductase (dhfr) and dihydropteroate synthase (dhps) modify responses to antifolate therapies which target these enzymes. However, the involvement of other genes which modify the availability of exogenous folate, for example, has been proposed. Here, we used short-read whole-genome re-sequencing to determine the mutations in a clone of the rodent malaria parasite, Plasmodium chabaudi, which has altered susceptibility to both sulphadoxine and pyrimethamine. This clone bears a previously identified S106N mutation in dhfr and no mutation in dhps. Instead, three additional point mutations in genes on chromosomes 2, 13 and 14 were identified. The mutated gene on chromosome 13 (mdr2 K392Q) encodes an ABC transporter. Because Quantitative Trait Locus analysis previously indicated an association of genetic markers on chromosome 13 with responses to individual and combined antifolates, MDR2 is proposed to modulate antifolate responses, possibly mediated by the transport of folate intermediates. (C) 2010 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.
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