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Blood, 15 November 2004, Vol. 104, No. 10, pp. 3372-3377. Prepublished online as a Blood First Edition Paper on June 17, 2004; DOI 10.1182/blood-2004-03-1084. This Article Full Text Full Text (PDF) All Versions of this Article: 2004-03-1084v1 104/10/3372    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Biagini, G. A. Articles by Bray, P. G. Search for Related Content PubMed PubMed Citation Articles by Biagini, G. A. Articles by Bray, P. G. Related Collections Red Cells Free Research Articles Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  RED CELLS Characterization of the choline carrier of Plasmodium falciparum: a route for the selective delivery of novel antimalarial drugs Giancarlo A. Biagini, Erica M. Pasini, Ruth Hughes, Harry P. De Koning, Henri J. Vial, Paul M. O'Neill, Stephen A. Ward, and Patrick G. Bray From the Molecular and Biochemical Parasitology Group, Liverpool School of Tropical Medicine, England; Division of Infection and Immunity, Institute of Biomedical and Life Sciences, University of Glasgow, Scotland; and Centre National de la Recherche Scientifique (CNRS) Unité Mixte de Recherche (UMR) 5539, Université Montpellier II, France. New drugs are urgently needed to combat the growing problem of drug resistance in Plasmodium falciparum malaria. The infected erythrocyte is a multicompartmental system, and its transporters are of interest as drug targets in their own right and as potential routes for the delivery of antimalarial drugs. Choline is an important nutrient that penetrates infected erythrocyte membranes through the endogenous carrier and through parasite-induced permeability pathways, but nothing is known about its transport into the intracellular parasite. Here we present the first characterization of choline transport across the parasite membrane. Transport exhibits Michaelis-Menten kinetics with an apparent Km of 25.0 ± 3.5 µM for choline. The carrier is inhibitor-sensitive, temperature-dependent, and Na+-independent, and it is driven by the proton-motive force. Highly active bis-amidine and bis-quaternary ammonium compounds are also known to penetrate the host erythrocyte membrane through parasite-induced permeability pathways. Here, we demonstrate that the parasite choline transporter mediates the delivery of these compounds to the intracellular parasite. Thus, the induced permeability pathways in the host erythrocyte membrane and the parasite choline transporter described here form a cooperative transport system that shows great promise for the selective targeting of new agents for the chemotherapy of malaria. (Blood. 2004;104: 3372-3377) CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: A choline "vacuum cleaner" Virgilio L. Lew Blood 2004 104: 3006-3007. [Full Text] [PDF] This article has been cited by other articles: M.-F. Penet, F. Kober, S. Confort-Gouny, Y. Le Fur, C. Dalmasso, N. Coltel, A. Liprandi, J.-M. Gulian, G. E. Grau, P. J. Cozzone, et al. Magnetic Resonance Spectroscopy Reveals an Impaired Brain Metabolic Profile in Mice Resistant to Cerebral Malaria Infected with Plasmodium berghei ANKA J. Biol. Chem., May 11, 2007; 282(19): 14505 - 14514. [Abstract] [Full Text] [PDF] V. Choubey, P. Maity, M. Guha, S. Kumar, K. Srivastava, S. K. Puri, and U. Bandyopadhyay Inhibition of Plasmodium falciparum Choline Kinase by Hexadecyltrimethylammonium Bromide: a Possible Antimalarial Mechanism Antimicrob. Agents Chemother., February 1, 2007; 51(2): 696 - 706. [Abstract] [Full Text] [PDF] G. Lisk and S. A. Desai The Plasmodial Surface Anion Channel Is Functionally Conserved in Divergent Malaria Parasites Eukaryot. Cell, December 1, 2005; 4(12): 2153 - 2159. [Abstract] [Full Text] [PDF] G. Pessi, J.-Y. Choi, J. M. Reynolds, D. R. Voelker, and C. B. Mamoun In Vivo Evidence for the Specificity of Plasmodium falciparum Phosphoethanolamine Methyltransferase and Its Coupling to the Kennedy Pathway J. Biol. Chem., April 1, 2005; 280(13): 12461 - 12466. [Abstract] [Full Text] [PDF]

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