Chloroquine resistance in Plasmodium chabaudi: are chloroquine-resistance transporter (crt) and multi-drug resistance (mdr1) orthologues involved?

Paul Hunt, Pedro V L Cravo, Paul Donleavy, Jane M-R Carlton, David Walliker

Research output: Contribution to journalArticlepeer-review

46 Citations (Scopus)


We have identified in the rodent malaria parasite Plasmodium chabaudi orthologues of two Plasmodium falciparum genes, pfcrt and pfmdr1 which have been implicated as determinants of chloroquine resistance in the latter species. The sequences of the P. chabaudi genes, denoted, respectively, pccg10 and pcmdr1, were first determined in the chloroquine-sensitive clone AS, and found to be highly similar to those of P. falciparum. For pccg10, there was a nucleotide sequence identity of 68.6% and amino acid sequence identity of 75.1% within the predicted coding region. For pcmdr1, the sequence identities were 75.0% (nucleotide) and 78.1% (amino acid). The sequences of the genes were then determined in three P. chabaudi clones selected from clone AS which possessed three different levels of resistance to chloroquine. The sequences of both genes in all mutants were found to be identical to those of the sensitive AS from which they had been derived. Polymorphic sites were found in both genes between the AS clones and a genetically unrelated sensitive clone AJ. Analysis of genetic crosses between AJ and resistant AS clones showed no linkage between inherited parental alleles of pccrt and pcmdr1 and drug responses of the cloned progeny. This showed that neither of these genes, nor genes closely linked to them, were determinants of the chloroquine resistance in the P. chabaudi mutants.

Original languageEnglish
Pages (from-to)27-35
Number of pages9
JournalMolecular And Biochemical Parasitology
Issue number1
Publication statusPublished - Jan 2004


  • Amino Acid Sequence
  • Animals
  • Antimalarials
  • Chloroquine
  • DNA, Protozoan
  • Drug Resistance
  • Genes, MDR
  • Genes, Protozoan
  • Membrane Transport Proteins
  • Molecular Sequence Data
  • Parasitic Sensitivity Tests
  • Plasmodium chabaudi
  • Plasmodium falciparum
  • Protozoan Proteins
  • Sequence Alignment
  • Sequence Analysis, DNA
  • Sequence Homology
  • Journal Article
  • Research Support, Non-U.S. Gov't


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