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Antimicrobial Agents and Chemotherapy, August 2003, p. 2393-2396, Vol. 47, No. 8
0066-4804/03/$08.00+0     DOI: 10.1128/AAC.47.8.2393-2396.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Reversal of Mefloquine and Quinine Resistance in Plasmodium falciparum with NP30

Michelle Ciach,1 Kathleen Zong,2 Kevin C. Kain,1,2 and Ian Crandall2,3*

Tropical Disease Unit, Toronto General Hospital,2 Institute of Medical Sciences, Department of Medicine,1 Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada3

Received 18 July 2002/ Returned for modification 20 November 2002/ Accepted 28 April 2003

Quinoline resistance in malaria is frequently compared with P-glycoprotein-mediated multidrug resistance (mdr) in mammalian cells. We have previously reported that nonylphenolethoxylates, such as NP30, are potential Plasmodium falciparum P-glycoprotein substrates and drug efflux inhibitors. We used in vitro assays to compare the ability of verapamil and NP30 to sensitize two parasite isolates to four quinolines: chloroquine (CQ), mefloquine (MF), quinine (QN), and quinidine (QD). NP30 was able to sensitize (reversal, >80%) P. falciparum to MF, QN, QD, and, to a lesser extent, CQ. The presence of 2 µM verapamil had no effect on mefloquine resistance; however, the presence of verapamil modulated the activities of QN and QD in a manner parallel to that observed for CQ. Genetic analysis of putative quinoline resistance genes did not suggest an association between known point mutations in pfcrt and pfmdr1 and NP30 sensitization activity. We conclude that the sensitization action of NP30 is distinct both phenotypically and genotypically from that of verapamil.

* Corresponding author. Mailing address: Clinical Science Division, Rm. 7316, Medical Sciences Building, 1 Kings College Circle, Toronto, Ontario M5S 1A8, Canada. Phone: (416) 978-0356. Fax: (416) 978-8765. E-mail: ian.crandall{at}utoronto.ca.

Antimicrobial Agents and Chemotherapy, August 2003, p. 2393-2396, Vol. 47, No. 8
0066-4804/03/$08.00+0     DOI: 10.1128/AAC.47.8.2393-2396.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Masseno, V., Muriithi, S., Nzila, A. (2009). In Vitro Chemosensitization of Plasmodium falciparum to Antimalarials by Verapamil and Probenecid. Antimicrob. Agents Chemother. 53: 3131-3134 [Abstract] [Full Text]  


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