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  • The EMBO Journal (2006) 25, 3000 - 3011
  • doi:10.1038/sj.emboj.7601203

Published online: 22 June 2006

Genetic linkage of pfmdr1 with food vacuolar solute import in Plasmodium falciparum

Petra Rohrbach1, Cecilia P Sanchez1, Karen Hayton2, Oliver Friedrich3, Jigar Patel4, Amar Bir Singh Sidhu5, Michael T Ferdig4, David A Fidock5 and Michael Lanzer1

  1. Hygiene Institut, Abteilung Parasitologie, Universitätsklinikum Heidelberg, Heidelberg, Germany
  2. Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA
  3. Medical Biophysics, Institute of Physiology and Pathophysiology, University of Heidelberg, Heidelberg, Germany
  4. Department of Biological Sciences, University of Notre Dame, IN, USA
  5. Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY, USA

Correspondence to:

Michael Lanzer, Hygiene Institut, Abteilung Parasitologie, Universitätsklinikum Heidelberg, Im Neuenheimer Feld 324, 69120 Heidelberg, Germany. Tel.: +49 6221 567845; Fax: +49 6221 564643; E-mail: michael_lanzer@med.uni-heidelberg.de

Received 12 January 2006; Accepted 29 May 2006

The P-glycoprotein homolog of the human malaria parasite Plasmodium falciparum (Pgh-1) has been implicated in decreased susceptibility to several antimalarial drugs, including quinine, mefloquine and artemisinin. Pgh-1 mainly resides within the parasite's food vacuolar membrane. Here, we describe a surrogate assay for Pgh-1 function based on the subcellular distribution of Fluo-4 acetoxymethylester and its free fluorochrome. We identified two distinct Fluo-4 staining phenotypes: preferential staining of the food vacuole versus a more diffuse staining of the entire parasite. Genetic, positional cloning and pharmacological data causatively link the food vacuolar Fluo-4 phenotype to those Pgh-1 variants that are associated with altered drug responses. On the basis of our data, we propose that Pgh-1 imports solutes, including certain antimalarial drugs, into the parasite's food vacuole. The implications of our findings for drug resistance mechanisms and testing are discussed.

  • Keywords:

    • drug transport,
    • Fluo-4,
    • malaria,
    • P-glycoprotein