[Contribution of molecular genetics to the understanding of chemoresistance of Plasmodium falciparum].
Resistance to pyrimethamine and proguanil is due to a single point mutation in the gene that codes for dihydrofolate reductase. A single mutation gives rise to resistance to only one of the drugs. Resistance to both drugs results from several mutations. Chloroquine resistance phenotype is due to a rapid efflux of the drug from the parasite's digestive vacuole. This efflux is associated with a transmembrane permeability glycoprotein, or P-gp, which is similar to the protein implicated in the multidrug resistant phenotype of some cancer cells. However, one or several other poorly understood major gene(s) may be involved. Drugs which can inhibit the supposed affinity of P-gp for chloroquine are under study.
Centre National de Référence pour la Chimiosensibilité du Paludisme, Hôpital Bichat - Claude-Bernard, Paris.
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Le Bras
L K
LK
Basco
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Cremer
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Charmot
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000818:Animals; D002738:Chloroquine / Q000494:pharmacology*; D004351:Drug Resistance / Q000235:genetics; D005493:Folic Acid Antagonists / Q000494:pharmacology*; D008562:Membrane Glycoproteins / Q000502:physiology; D008967:Molecular Biology; D009154:Mutation; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000235:genetics* / Q000378:metabolism; D011739:Pyrimethamine / Q000494:pharmacology*; D014227:Triazines / Q000494:pharmacology*
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D005493:Folic Acid Antagonists; D008562:Membrane Glycoproteins; D014227:Triazines; C073266:cycloguanil pamoate; D002738:Chloroquine; D011739:Pyrimethamine
Apport de la génétique moléculaire à la compréhension des chimio-résistances de Plasmodium falciparum.