title: Quinine localizes to a non-acidic compartment within the food vacuole of the malaria parasite Plasmodium falciparum.
abstract: BACKGROUND
  The naturally fluorescent compound quinine has long been used to treat malaria infections. Although some evidence suggests that quinine acts in the parasite food vacuole, the mechanism of action of quinine has not yet been resolved. The Plasmodium falciparum multidrug resistance (pfmdr1) gene encodes a food vacuolar membrane transporter and has been linked with parasite resistance to quinine. The effect of multiple pfmdr1 copies on the subcellular localization of quinine was explored.
  
  
  METHODS
  Fluorescence microscopy was used to evaluate the subcellular localization of quinine in parasites containing different pfmdr1 copy numbers to determine if copy number of the gene affects drug localization. The acidotropic dye LysoTracker Red was used to label the parasite food vacuole. Time-lapse images were taken to determine quinine localization over time following quinine exposure.
  
  
  RESULTS
  Regardless of pfmdr1 copy number, quinine overlapped with haemozoin but did not colocalize with LysoTracker Red, which labeled the acidic parasite food vacuole.
  
  
  CONCLUSIONS
  Quinine localizes to a non-acidic compartment within the food vacuole possibly haemozoin. Pfmdr1 copy number does not affect quinine subcellular localization.
authors.affiliation: Department of Epidemiology, University of North Carolina at Chapel Hill, Campus Box 7435, Chapel Hill, NC 27599-7435, USA.
authors.forename: Elaine B
authors.initials: EB
authors.lastname: Bohórquez
authors.forename: Michael
authors.initials: M
authors.lastname: Chua
authors.forename: Steven R
authors.initials: SR
authors.lastname: Meshnick
mesh_terms: D000962:Antimalarials / Q000032:analysis*; D004351:Drug Resistance; D018628:Gene Dosage; D008856:Microscopy, Fluorescence; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics / Q000378:metabolism; D050505:Mutant Proteins / Q000235:genetics / Q000378:metabolism; D010963:Plasmodium falciparum / Q000737:chemistry* / Q000187:drug effects*; D011803:Quinine / Q000032:analysis*; D059008:Time-Lapse Imaging; D014617:Vacuoles / Q000737:chemistry*
chemical_list: D000962:Antimalarials; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D050505:Mutant Proteins; D011803:Quinine; C513498:Mdr1 protein, Plasmodium falciparum