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Open Access Highly Accessed Research

Quinine localizes to a non-acidic compartment within the food vacuole of the malaria parasite Plasmodium falciparum

Elaine B Bohórquez1, Michael Chua2 and Steven R Meshnick3*

Author Affiliations

1 3113 Michael Hooker Research Center, Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA

2 6129 Thurston Bowles, Michael Hooker Microscopy Facility, University of North Carolina at Chapel Hill, Campus Box 7248, Chapel Hill, NC, 27599-7248, USA

3 3301 Michael Hooker Research Center, Department of Epidemiology, University of North Carolina at Chapel Hill, Campus Box 7435, Chapel Hill, NC 27599-7435, USA

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Malaria Journal 2012, 11:350  doi:10.1186/1475-2875-11-350

Published: 22 October 2012

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.

Keywords:
Quinine; Plasmodium falciparum; Pfmdr1; Copy number