The central role of mosquito cytochrome P450 CYP6Zs in insecticide detoxification revealed by functional expression and structural modelling.

Détails

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Etat: Public
Version: Final published version
ID Serval
serval:BIB_3BD092DD43F6
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
The central role of mosquito cytochrome P450 CYP6Zs in insecticide detoxification revealed by functional expression and structural modelling.
Périodique
Biochemical Journal
Auteur(s)
Chandor-Proust A., Bibby J., Régent-Kloeckner M., Roux J., Guittard-Crilat E., Poupardin R., Riaz M.A., Paine M., Dauphin-Villemant C., Reynaud S., David J.P.
ISSN
1470-8728 (Electronic)
ISSN-L
0264-6021
Statut éditorial
Publié
Date de publication
2013
Volume
455
Numéro
1
Pages
75-85
Langue
anglais
Résumé
The resistance of mosquitoes to chemical insecticides is threatening vector control programmes worldwide. Cytochrome P450 monooxygenases (CYPs) are known to play a major role in insecticide resistance, allowing resistant insects to metabolize insecticides at a higher rate. Among them, members of the mosquito CYP6Z subfamily, like Aedes aegypti CYP6Z8 and its Anopheles gambiae orthologue CYP6Z2, have been frequently associated with pyrethroid resistance. However, their role in the pyrethroid degradation pathway remains unclear. In the present study, we created a genetically modified yeast strain overexpressing Ae. aegypti cytochrome P450 reductase and CYP6Z8, thereby producing the first mosquito P450-CPR (NADPH-cytochrome P450-reductase) complex in a yeast recombinant system. The results of the present study show that: (i) CYP6Z8 metabolizes PBAlc (3-phenoxybenzoic alcohol) and PBAld (3-phenoxybenzaldehyde), common pyrethroid metabolites produced by carboxylesterases, producing PBA (3-phenoxybenzoic acid); (ii) CYP6Z8 transcription is induced by PBAlc, PBAld and PBA; (iii) An. gambiae CYP6Z2 metabolizes PBAlc and PBAld in the same way; (iv) PBA is the major metabolite produced in vivo and is excreted without further modification; and (v) in silico modelling of substrate-enzyme interactions supports a similar role of other mosquito CYP6Zs in pyrethroid degradation. By playing a pivotal role in the degradation of pyrethroid insecticides, mosquito CYP6Zs thus represent good targets for mosquito-resistance management strategies.
Mots-clé
Aedes/drug effects, Aedes/enzymology, Animals, Anopheles gambiae/drug effects, Anopheles gambiae/enzymology, Benzaldehydes/chemistry, Benzaldehydes/metabolism, Benzoates/metabolism, Cytochrome P-450 Enzyme System/chemistry, Cytochrome P-450 Enzyme System/genetics, Escherichia coli/enzymology, Escherichia coli/genetics, Genetic Engineering, Insect Proteins/chemistry, Insect Proteins/genetics, Insect Vectors/drug effects, Insect Vectors/enzymology, Insecticide Resistance/drug effects, Insecticide Resistance/genetics, Insecticides/chemistry, Insecticides/metabolism, Isoenzymes/chemistry, Isoenzymes/genetics, Metabolic Detoxication, Drug, Molecular Docking Simulation, NADPH-Ferrihemoprotein Reductase/chemistry, NADPH-Ferrihemoprotein Reductase/genetics, Oxidation-Reduction, Pyrethrins/chemistry, Pyrethrins/metabolism, Saccharomyces cerevisiae/drug effects, Saccharomyces cerevisiae/enzymology
Pubmed
Web of science
Open Access
Oui
Création de la notice
12/02/2014 13:08
Dernière modification de la notice
20/08/2019 13:31
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