Evidence That Mutant PfCRT Facilitates the Transmission to Mosquitoes of Chloroquine-Treated Plasmodium Gametocytes
- 15 January 2011
- journal article
- research article
- Published by Oxford University Press (OUP) in The Journal of Infectious Diseases
- Vol. 203 (2) , 228-236
- https://doi.org/10.1093/infdis/jiq036
Abstract
Resistance of the human malarial parasite Plasmodium falciparum to the antimalarial drug chloroquine has rapidly spread from several independent origins and is now widely prevalent throughout the majority of malaria-endemic areas. Field studies have suggested that chloroquine-resistant strains might be more infective to mosquito vectors. To test the hypothesis that the primary chloroquine resistance determinant, mutations in PfCRT, facilitates parasite transmission under drug pressure, we have introduced a mutant or wild-type pfcrt allele into the rodent model malarial parasite Plasmodium berghei. Our results show that mutant PfCRT from the chloroquine-resistant 7G8 strain has no effect on asexual blood stage chloroquine susceptibility in vivo or ex vivo but confers a significant selective advantage in competitive mosquito infections in the presence of this drug, by protecting immature gametocytes from its lethal action. Enhanced infectivity to mosquitoes may have been a key factor driving the worldwide spread of mutant pfcrt.Keywords
This publication has 48 references indexed in Scilit:
- Amodiaquine Resistance in Plasmodium falciparum Malaria in Afghanistan Is Associated with the pfcrt SVMNT Allele at Codons 72 to 76Antimicrobial Agents and Chemotherapy, 2010
- Identification of a Mutant PfCRT-Mediated Chloroquine Tolerance Phenotype in Plasmodium falciparumPLoS Pathogens, 2010
- A semi-automated method for counting fluorescent malaria oocysts increases the throughput of transmission blocking studiesMalaria Journal, 2010
- Geographic patterns of Plasmodium falciparum drug resistance distinguished by differential responses to amodiaquine and chloroquineProceedings of the National Academy of Sciences, 2009
- Artemisinin-based combination therapies: a vital tool in efforts to eliminate malariaNature Reviews Microbiology, 2009
- Chloroquine resistance before and after its withdrawal in KenyaMalaria Journal, 2009
- A systematic review and meta-analysis of evidence for correlation between molecular markers of parasite resistance and treatment outcome in falciparum malariaMalaria Journal, 2009
- In Vivo Selection ofPlasmodium falciparumParasites Carrying the Chloroquine-SusceptiblepfcrtK76 Allele after Treatment with Artemether-Lumefantrine in AfricaThe Journal of Infectious Diseases, 2009
- Chloroquine Resistance-Conferring Mutations in pfcrt Give Rise to a Chloroquine-Associated H + Leak from the Malaria Parasite's Digestive VacuoleAntimicrobial Agents and Chemotherapy, 2008
- Chloroquine: Physiological Basis of Drug Resistance in Plasmodium bergheiScience, 1966