Open AccessPlasmodium falciparum Na + /H + Exchanger 1 Transporter Is Involved in Reduced Susceptibility to Quinine
Author(s) -
MarieClaire Henry,
Sébastien Briolant,
Agnès Zettor,
Stéphane Pelleau,
Meïli Baragatti,
Eric Baret,
Joël Mosnier,
Rémy Amalvict,
Thierry Fusaı̈,
Christophe Rogier,
Bruno Pradines
Publication year - 2009
Publication title -
antimicrobial agents and chemotherapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.07
H-Index - 259
eISSN - 1070-6283
pISSN - 0066-4804
DOI - 10.1128/aac.01243-08
Subject(s) - plasmodium falciparum , quinine , microsatellite , biology , microbiology and biotechnology , genetics , virology , chemistry , gene , malaria , allele , immunology
Polymorphisms in thePlasmodium falciparum crt (Pfcrt ), Pfmdr1 , and Pfmrp genes were not significantly associated with quinine (QN) 50% inhibitory concentrations (IC50 s) in 23 strains ofPlasmodium falciparum . An increased number of DNNND repeats in Pfnhe-1 microsatellite ms4760 was associated with an increased IC50 of QN (P = 0.0007). Strains with only one DNNND repeat were more susceptible to QN (mean IC50 of 154 nM). Strains with two DNNND repeats had intermediate susceptibility to QN (mean IC50 of 548 nM). Strains with three DNNND repeats had reduced susceptibility to QN (mean IC50 of 764 nM). Increased numbers of NHNDNHNNDDD repeats were associated with a decreased IC50 of QN (P = 0.0020). Strains with profile 7 for Pfnhe-1 ms4760 (ms4760-7) were significantly associated with reduced QN susceptibility (mean IC50 of 764 nM). The determination of DNNND and NHNDNHNNDDD repeats in Pfnhe-1 ms4760 could be a good marker of QN resistance and provide an attractive surveillance method to monitor temporal trends inP. falciparum susceptibility to QN. The validity of the markers should be further supported by analyzing more isolates.