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Antimicrobial Agents and Chemotherapy, May 2009, p. 1926-1930, Vol. 53, No. 5
0066-4804/09/$08.00+0     doi:10.1128/AAC.01243-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

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

Maud Henry,1 Sébastien Briolant,1 Agnès Zettor,1 Stéphane Pelleau,2 Meili Baragatti,1 Eric Baret,1 Joel Mosnier,1 Rémy Amalvict,1 Thierry Fusai,1 Christophe Rogier,1 and Bruno Pradines1,3*

Unité de Recherche en Biologie et Epidémiologie Parasitaires, Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes, UMR 6236, Institut de Médecine Tropicale du Service de Santé des Armées, Marseille, France,1 Unité de Recherche en Physiologie et Pharmacocinétique Parasitaires, UMR-MD3 Relations Hôte-Parasites, Pharmacologie et Thérapeutique, Institut de Médecine Tropicale du Service de Santé des Armées, Marseille, France,2 Centre National de Référence du Paludisme, Marseille, France3

Received 18 September 2008/ Returned for modification 30 November 2008/ Accepted 24 February 2009

Polymorphisms in the Plasmodium falciparum crt (Pfcrt), Pfmdr1, and Pfmrp genes were not significantly associated with quinine (QN) 50% inhibitory concentrations (IC50s) in 23 strains of Plasmodium 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 in P. falciparum susceptibility to QN. The validity of the markers should be further supported by analyzing more isolates.

* Corresponding author. Mailing address: Unité de Recherche en Biologie et Epidémiologie Parasitaires, Institut de Médecine Tropicale du Service de Santé des Armées, Allée du Médecin Colonel Jamot, Parc le Pharo, BP 60109, 13262 Marseille Cedex 07, Marseille, France. Phone: 33 4 91 15 01 10. Fax: 33 4 91 15 01 64. E-mail: bruno.pradines{at}free.fr

{triangledown} Published ahead of print on 9 March 2009.

Antimicrobial Agents and Chemotherapy, May 2009, p. 1926-1930, Vol. 53, No. 5
0066-4804/09/$08.00+0     doi:10.1128/AAC.01243-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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