Dissecting the components of quinine accumulation in Plasmodium falciparum

Molecular Microbiology
Cecilia P SanchezMichael Lanzer

Abstract

Although quinine, the active ingredient of chinchona bark, has been used in the treatment of malaria for several centuries, there is little information regarding the interactions of this drug with the human malaria parasite Plasmodium falciparum. To better understand quinine's mode of action and the mechanism underpinning reduced responsiveness, we have investigated the factors that contribute to quinine accumulation by parasites that differ in their susceptibility to quinine. Interestingly, passive distribution, in accordance with the intracellular pH gradients, and intracellular binding could account for only a small fraction of the high amount of quinine accumulated by the parasites investigated. The results of trans-stimulation kinetics suggest that high accumulation of quinine is brought about by a carrier-mediated import system. This import system seems to be weakened in parasites with reduced quinine susceptibility. Other data show that polymorphisms within PfCRT are causatively linked with an increased verapamil-sensitive quinine efflux that, depending on the genetic background, resulted in reduced quinine accumulation. The polymorphisms within PfMDR1 investigated did not affect quinine accumulation. Our data are consis...Continue Reading

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Citations

Oct 1, 2011·Molecular Genetics and Genomics : MGG·Sandra C Dos Santos, Isabel Sá-Correia
Mar 11, 2009·Antimicrobial Agents and Chemotherapy·Maud HenryBruno Pradines
Dec 16, 2010·Future Microbiology·Ingrid B Müller, John E Hyde
Jan 31, 2012·Cellular and Molecular Life Sciences : CMLS·Robert L SummersRowena E Martin
Apr 20, 2010·International Journal for Parasitology·Cecilia P SanchezMichael Lanzer
Sep 8, 2009·Trends in Parasitology·Wilfred D SteinMichael Lanzer
Aug 16, 2008·Experimental Parasitology·Karena L WallerThomas V McDonald
Nov 8, 2008·Molecular Microbiology·Kevin J SalibaKiaran Kirk
Dec 12, 2013·The Biochemical Journal·Kiaran Kirk, Adele M Lehane
Nov 19, 2014·Bioscience Reports·Rongwei TengKiaran Kirk
Mar 4, 2015·Proceedings of the National Academy of Sciences of the United States of America·Narinobu JugeYoshinori Moriyama
May 11, 2018·Chinese Medicine·Ru YanYijia Chen
Jan 27, 2012·ACS Chemical Biology·Katherine A de VilliersTanya le Roex

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