Chloroquine transport via the malaria parasite's chloroquine resistance transporter
- PMID: 19779197
- DOI: 10.1126/science.1175667
Chloroquine transport via the malaria parasite's chloroquine resistance transporter
Abstract
The emergence and spread of chloroquine-resistant Plasmodium falciparum malaria parasites has been a disaster for world health. Resistance is conferred by mutations in the Chloroquine Resistance Transporter (PfCRT), an integral membrane protein localized to the parasite's internal digestive vacuole. These mutations result in a marked reduction in the accumulation of chloroquine (CQ) by the parasite. However, the mechanism by which this occurs is unclear. We expressed both wild-type and resistant forms of PfCRT at the surface of Xenopus laevis oocytes. The resistant form of PfCRT transported CQ, whereas the wild-type protein did not. CQ transport via the mutant PfCRT was inhibited by CQ analogs and by the resistance-reverser verapamil. Thus, CQ resistance is due to direct transport of the drug via mutant PfCRT.
Similar articles
-
Functional characteristics of the malaria parasite's "chloroquine resistance transporter": implications for chemotherapy.Virulence. 2010 Jul-Aug;1(4):304-8. doi: 10.4161/viru.1.4.12012. Virulence. 2010. PMID: 21178460
-
Verapamil-Sensitive Transport of Quinacrine and Methylene Blue via the Plasmodium falciparum Chloroquine Resistance Transporter Reduces the Parasite's Susceptibility to these Tricyclic Drugs.J Infect Dis. 2016 Mar 1;213(5):800-10. doi: 10.1093/infdis/jiv509. Epub 2015 Oct 26. J Infect Dis. 2016. PMID: 26503982
-
Is PfCRT a channel or a carrier? Two competing models explaining chloroquine resistance in Plasmodium falciparum.Trends Parasitol. 2007 Jul;23(7):332-9. doi: 10.1016/j.pt.2007.04.013. Epub 2007 May 10. Trends Parasitol. 2007. PMID: 17493873 Review.
-
Diverse mutational pathways converge on saturable chloroquine transport via the malaria parasite's chloroquine resistance transporter.Proc Natl Acad Sci U S A. 2014 Apr 29;111(17):E1759-67. doi: 10.1073/pnas.1322965111. Epub 2014 Apr 11. Proc Natl Acad Sci U S A. 2014. PMID: 24728833 Free PMC article.
-
pfcrt is more than the Plasmodium falciparum chloroquine resistance gene: a functional and evolutionary perspective.Acta Trop. 2005 Jun;94(3):170-80. doi: 10.1016/j.actatropica.2005.04.004. Acta Trop. 2005. PMID: 15866507 Review.
Cited by
-
Probiotics: an alternative anti-parasite therapy.J Parasit Dis. 2024 Sep;48(3):409-423. doi: 10.1007/s12639-024-01680-4. Epub 2024 May 13. J Parasit Dis. 2024. PMID: 39145362 Review.
-
The Digestive Vacuole of the Malaria Parasite: A Specialized Lysosome.Pathogens. 2024 Feb 20;13(3):182. doi: 10.3390/pathogens13030182. Pathogens. 2024. PMID: 38535526 Free PMC article. Review.
-
Additional PfCRT mutations driven by selective pressure for improved fitness can result in the loss of piperaquine resistance and altered Plasmodium falciparum physiology.mBio. 2024 Jan 16;15(1):e0183223. doi: 10.1128/mbio.01832-23. Epub 2023 Dec 7. mBio. 2024. PMID: 38059639 Free PMC article.
-
pH-dependence of the Plasmodium falciparum chloroquine resistance transporter is linked to the transport cycle.Nat Commun. 2023 Jul 15;14(1):4234. doi: 10.1038/s41467-023-39969-2. Nat Commun. 2023. PMID: 37454114 Free PMC article.
-
Aurachins, Bacterial Antibiotics Interfering with Electron Transport Processes.Antibiotics (Basel). 2023 Jun 17;12(6):1067. doi: 10.3390/antibiotics12061067. Antibiotics (Basel). 2023. PMID: 37370386 Free PMC article. Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources