Plasmodium falciparum Na + /H + Exchanger 1 Transporter Is Involved in Reduced Susceptibility to Quinine

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Henry, Maud | Briolant, Sébastien | Zettor, Agnès | Pelleau, Stéphane | Baragatti, Meili | Baret, Eric | Mosnier, Joel | Amalvict, Rémy | Fusai, Thierry | Rogier, Christophe | Pradines, Bruno

Edité par CCSD ; American Society for Microbiology -

International audience. ABSTRACT Polymorphisms in the Plasmodium falciparum crt (Pf crt ), Pf mdr1 , and Pf mrp genes were not significantly associated with quinine (QN) 50% inhibitory concentrations (IC 50 s) in 23 strains of Plasmodium falciparum . An increased number of DNNND repeats in Pf nhe-1 microsatellite ms4760 was associated with an increased IC 50 of QN ( P = 0.0007). Strains with only one DNNND repeat were more susceptible to QN (mean IC 50 of 154 nM). Strains with two DNNND repeats had intermediate susceptibility to QN (mean IC 50 of 548 nM). Strains with three DNNND repeats had reduced susceptibility to QN (mean IC 50 of 764 nM). Increased numbers of NHNDNHNNDDD repeats were associated with a decreased IC 50 of QN ( P = 0.0020). Strains with profile 7 for Pf nhe-1 ms4760 (ms4760-7) were significantly associated with reduced QN susceptibility (mean IC 50 of 764 nM). The determination of DNNND and NHNDNHNNDDD repeats in Pf nhe-1 ms4760 could be a good marker of QN resistance and provide an attractive surveillance method to monitor temporal trends in P. falciparum susceptibility to QN. The validity of the markers should be further supported by analyzing more isolates.

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