Association between Polymorphisms in the Pf mdr6 Gene and Ex Vivo Susceptibility to Quinine in Plasmodium falciparum Parasites from Dakar, Senegal

Mathieu Gendrot; Silman Diawara; Marylin Madamet; Mame Bou Kounta; Sébastien Briolant; Khalifa Ababacar Wade; Mansour Fall; Nicolas Benoit; Aminata Nakoulima; Rémy Amalvict; Yaya Diémé; Bécaye Fall; Boubacar Wade; Bakary Diatta; Bruno Pradines

doi:10.1128/AAC.01183-16

Association between Polymorphisms in the Pf mdr6 Gene and Ex Vivo Susceptibility to Quinine in Plasmodium falciparum Parasites from Dakar, Senegal

Antimicrob Agents Chemother. 2017 Feb 23;61(3):e01183-16. doi: 10.1128/AAC.01183-16. Print 2017 Mar.

Authors

Mathieu Gendrot^{1

2}, Silman Diawara³, Marylin Madamet^{2

4

5}, Mame Bou Kounta⁶, Sébastien Briolant^{1

2

7

8}, Khalifa Ababacar Wade⁶, Mansour Fall⁹, Nicolas Benoit^{2

4

5}, Aminata Nakoulima¹⁰, Rémy Amalvict^{2

4

5}, Yaya Diémé³, Bécaye Fall³, Boubacar Wade¹¹, Bakary Diatta^{9

11}, Bruno Pradines^{12

2

3

5}

Affiliations

¹ Unité de Parasitologie et d'Entomologie, Département des Maladies Infectieuses, Institut de Recherche Biomédicale des Armées, Marseille, France.
² Aix Marseille Université, Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes, UM 63, CNRS 7278, IRD 198, INSERM 1095, Marseille, France.
³ Laboratoire d'étude de la chimiosensibilité du paludisme, Fédération des laboratoires, Hôpital Principal de Dakar, Dakar, Senegal.
⁴ Equipe résidente de recherche en infectiologie tropicale, Institut de Recherche Biomédicale des Armées, Hôpital d'instruction des armées, Marseille, France.
⁵ Centre national de référence du Paludisme, Marseille, France.
⁶ Service des Urgences, Hôpital Principal de Dakar, Dakar, Senegal.
⁷ Direction Interarmées du Service de Santé, Cayenne, Guyane, France.
⁸ Laboratoire de Parasitologie, Institut Pasteur de la Guyane, Cayenne, Guyane, France.
⁹ Service de Réanimation Médicale, Hôpital Principal de Dakar, Dakar, Senegal.
¹⁰ Service de Pédiatrie, Hôpital Principal de Dakar, Dakar, Senegal.
¹¹ Chefferie, Hôpital Principal de Dakar, Dakar, Senegal.
¹² Unité de Parasitologie et d'Entomologie, Département des Maladies Infectieuses, Institut de Recherche Biomédicale des Armées, Marseille, France [email protected].

Abstract

Polymorphisms and the overexpression of transporter genes, especially of the ATP-binding cassette superfamily, have been involved in antimalarial drug resistance. The objective of this study was to use 77 Senegalese Plasmodium falciparum isolates to evaluate the association between the number of Asn residues in the polymorphic microsatellite region of the Plasmodium falciparum multidrug resistance 6 gene (Pfmdr6) and the ex vivo susceptibility to antimalarials. A significant association was observed between the presence of 7 or 9 Asn repeats and reduced susceptibility to quinine.

Keywords: Plasmodium falciparum; antimalarial drug; in vitro; malaria; molecular marker; resistance.

MeSH terms

ATP-Binding Cassette Transporters / genetics*
Amodiaquine / analogs & derivatives
Amodiaquine / pharmacology
Antimalarials / pharmacology*
Artemisinins / pharmacology
Artesunate
Asparagine / metabolism
Chloroquine / pharmacology
Doxycycline / pharmacology
Drug Resistance / genetics*
Ethanolamines / pharmacology
Fluorenes / pharmacology
Gene Expression
Humans
Inhibitory Concentration 50
Lumefantrine
Malaria, Falciparum / parasitology
Mefloquine / pharmacology
Naphthyridines / pharmacology
Plasmodium falciparum / drug effects
Plasmodium falciparum / genetics*
Plasmodium falciparum / growth & development
Plasmodium falciparum / isolation & purification
Polymorphism, Genetic*
Protein Isoforms / genetics
Protozoan Proteins / genetics*
Quinine / pharmacology*
Quinolines / pharmacology
Repetitive Sequences, Amino Acid
Senegal

Substances

ATP-Binding Cassette Transporters
Antimalarials
Artemisinins
Ethanolamines
Fluorenes
Naphthyridines
Protein Isoforms
Protozoan Proteins
Quinolines
mdr gene protein, Plasmodium
Amodiaquine
Artesunate
artenimol
Asparagine
desethylamodiaquine
Chloroquine
piperaquine
Quinine
Lumefantrine
Doxycycline
pyronaridine
Mefloquine