Drug resistance and the P-glycoprotein homologues of Plasmodium falciparum.
The chloroquine resistance phenotype of Plasmodium falciparum shares many similarities to multi-drug resistance in tumour cells and this has led to the identification of two mdr-like genes (pfmdr1, pfmdr2) from this human pathogen. The pfmdr1 gene has been linked to the chloroquine resistance phenotype, although a genetic cross appears to contradict these results. Analysis of drug resistant mutants selected in vitro has shown that the level of expression of the pfmdr1 gene can affect resistance to chloroquine, mefloquine, halofantrine and quinine. Mefloquine isolates from the field appear to always contain amplified levels of the pfmdr1 gene and also overexpress the transcript. They are also resistant to halofantrine suggesting a true multi-drug resistant phenotype.
Cowman
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Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia.
Karcz
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D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics*; D002738:Chloroquine / Q000494:pharmacology; D004351:Drug Resistance; D015870:Gene Expression; D015767:Mefloquine / Q000494:pharmacology; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000378:metabolism; D010641:Phenotype; D015800:Protozoan Proteins / Q000235:genetics* / Q000378:metabolism / Q000648:ultrastructure
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D015800:Protozoan Proteins; D002738:Chloroquine; D015767:Mefloquine