The impact of antimalarial drug resistance mutations on parasite fitness, and its implications for the evolution of resistance.
It is widely assumed in genetics that most mutations disrupt metabolism to some extent, and are consequently likely to be disadvantageous for the organisms that inherit them. This may apply to mutations encoding drug resistance in malaria, where the mutation may be disadvantageous in the absence of the drug, imposing a genetic 'cost' of resistance. We review several lines of evidence suggesting that such costs do occur, that they may be relatively large, and review their likely impact on the evolution of drug resistance in the malaria parasite Plasmodium falciparum.
Hastings
Ian M
IM
Liverpool School of Tropical Medicine, Pembroke Place, Liverpool L3 5QA, UK. hastings@liv.ac.uk
Donnelly
Martin J
MJ
D000818:Animals; D000962:Antimalarials / Q000627:therapeutic use*; D004351:Drug Resistance / Q000235:genetics*; D019143:Evolution, Molecular; D006801:Humans; D008288:Malaria / Q000188:drug therapy*; D009154:Mutation; D010963:Plasmodium falciparum / Q000187:drug effects / Q000201:enzymology / Q000235:genetics; D013762:Tetrahydrofolate Dehydrogenase / Q000235:genetics
D000962:Antimalarials; C098921:dihydrofolate reductase type II; D013762:Tetrahydrofolate Dehydrogenase