Plasmodium falciparum Na+/H+ exchanger 1 transporter is involved in reduced susceptibility to quinine.
Polymorphisms in the Plasmodium falciparum crt (Pfcrt), Pfmdr1, and Pfmrp 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 Pfnhe-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 Pfnhe-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 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.
Henry
Maud
M
Unité de Recherche en Biologie et Epidémiologie Parasitaires, Institut de Médecine Tropicale du Service de Santé des Armées, UMR 6236, Allée du Médecin Colonel Jamot, Parc le Pharo, BP 60109, 13262 Marseille Cedex 07, Marseille, France.
Briolant
Sébastien
S
Zettor
Agnès
A
Pelleau
Stéphane
S
Baragatti
Meili
M
Baret
Eric
E
Mosnier
Joel
J
Amalvict
Rémy
R
Fusai
Thierry
T
Rogier
Christophe
C
Pradines
Bruno
B
D000818:Animals; D000962:Antimalarials / Q000494:pharmacology*; D004351:Drug Resistance / Q000235:genetics*; D006801:Humans; D016778:Malaria, Falciparum / Q000469:parasitology; D018895:Microsatellite Repeats / Q000235:genetics; D021261:Parasitic Sensitivity Tests; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D011110:Polymorphism, Genetic; D015800:Protozoan Proteins / Q000737:chemistry / Q000235:genetics; D011803:Quinine / Q000494:pharmacology*; D017923:Sodium-Hydrogen Exchangers / Q000737:chemistry / Q000235:genetics*
D000962:Antimalarials; D015800:Protozoan Proteins; D017923:Sodium-Hydrogen Exchangers; C069139:growth factor-activatable Na-H exchanger NHE-1; D011803:Quinine