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Home / Publications / Whole genome re-sequencing identifies a mutation in an ABC transporter (mdr2) in a Plasmodium chabaudi clone with altered susceptibility to antifolate drugs?

Whole genome re-sequencing identifies a mutation in an ABC transporter (mdr2) in a Plasmodium chabaudi clone with altered susceptibility to antifolate drugs?

  • Authors: Cravo P, Henriques G, Hunt P, Martinelli A
  • Journal: International Journal for Parasitology
  • Link: http://www.ncbi.nlm.nih.gov/pubmed/?term=Whole+genome+re-sequencing+identifies+a+mutation+in+an+ABC+transporter+(mdr2)+in+a+Plasmodium+chabaudi+clone+with+altered+susceptibility+to+antifolate+drugs%3F.

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 intermedia

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About GHTM

GHTM is a R&D Unit that brings together researchers with a track record in Tropical Medicine and International & Global Health. It aims at strengthening Portugal's role as a leading partner in the development and implementation of a global health research agenda. Our evidence-based interventions contribute to the promotion of equity in health and to improve the health of populations.

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