Role of pfmdr1 mutations on chloroquine resistance in Plasmodium falciparum isolates with pfcrt K76T from Papua New Guinea

Acta Tropica
Toshihiro MitaA Björkman

Abstract

The N86Y mutation in pfmdr1 is reported to play an additional role for the chloroquine resistance in Plasmodium falciparum isolates. However, not much has been done to clarify whether this mutation augments the level of chloroquine resistance in the isolates harboring pfcrt K76T mutation. We compared the in vitro chloroquine efficacy between pfcrt K76T mutant parasites with or without N86Y mutation from Papua New Guinea. A total of 57 isolates (4% sensitive, 14% borderline, and 82% resistant) were successfully tested in vitro for chloroquine sensitivity. We found a slightly higher effective concentration of chloroquine needed to inhibit P. falciparum by 50% (mean EC50=107 nM) in isolates with the pfcrt K76T+pfmdr1 N86Y than that in isolates with the pfcrt K76T+pfmdr1 N86 (EC50=88 nM), but this difference was not statistically significant. A significant non-random association was observed between the pfcrt K76T and pfmdr1 N86Y alleles. Our results suggest that the pfmdr1 N86Y mutation plays a compensatory role to chloroquine-resistant isolates under a chloroquine pressure while it may also augment the level of chloroquine resistance in the K76T parasites to a small extent.

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Citations

Jan 11, 2007·Antimicrobial Agents and Chemotherapy·Toshihiro MitaTakatoshi Kobayakawa
Apr 28, 2009·Parasitology International·Toshihiro MitaKiyoshi Kita
May 1, 2007·Infection, Genetics and Evolution : Journal of Molecular Epidemiology and Evolutionary Genetics in Infectious Diseases·Gabrielle HolmgrenAnders Björkman
Apr 8, 2006·Infection, Genetics and Evolution : Journal of Molecular Epidemiology and Evolutionary Genetics in Infectious Diseases·Toshihiro MitaAnders Björkman
Oct 5, 2011·Essays in Biochemistry·Philippe LeprohonMarc Ouellette
Jun 10, 2014·Infection, Genetics and Evolution : Journal of Molecular Epidemiology and Evolutionary Genetics in Infectious Diseases·Kshipra ChauhanAparup Das
Feb 23, 2011·Memórias do Instituto Oswaldo Cruz·Sasmita Kumari Das SutarAparup Das
Apr 2, 2015·Expert Review of Anti-infective Therapy·Lorenz von Seidlein, Arjen Dondorp

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