title: The function of two P450s, CYP9M10 and CYP6AA7, in the permethrin resistance of Culex quinquefasciatus.
abstract: Cytochrome P450 monooxygenases play a critical role in insecticide resistance by allowing resistant insects to metabolize insecticides. Previous studies revealed that two P450 genes, CYP9M10 and CYP6AA7, are not only up-regulated but also induced in resistant Culex mosquitoes. In this study, CYP9M10 and CYP6AA7 were separately co-expressed with cytochrome P450 reductase (CPR) in insect Spodoptera frugiperda (Sf9) cells using a baculovirus-mediated expression system and the enzymatic activity and metabolic ability of CYP9M10/CPR and CYP6AA7/CPR to permethrin and its metabolites, including 3-phenoxybenzoic alcohol (PBOH) and 3-phenoxybenzaldehyde (PBCHO), characterized. PBOH and PBCHO, both of which are toxic to Culex mosquito larvae, can be further metabolized by CYP9M10/CPR and CYP6AA7/CPR, with the ultimate metabolite identified here as PBCOOH, which is considerably less toxic to mosquito larvae. A cell-based MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) cytotoxicity assay revealed that Sf9 cells expressing CYP9M10/CPR or CYP6AA7/CPR increased the cell line's tolerance to permethrin, PBOH, and PBCHO. This study confirms the important role played by CYP9M10 and CYP6AA7 in the detoxification of permethrin and its metabolites PBOH and PBCHO.
authors.affiliation: Department of Entomology and Plant Pathology, Auburn University, Auburn, AL, 36849, USA.|Department of Honeybee Protection and Biosafety, Institute of Apicultural Research, Chinese Academy of Agricultural Sciences, No. 1 Beigou Xiangshan, Haidian District, Beijing, 100093, P.R. China.
authors.forename: Youhui
authors.initials: Y
authors.lastname: Gong
authors.affiliation: Department of Entomology and Plant Pathology, Auburn University, Auburn, AL, 36849, USA.
authors.forename: Ting
authors.initials: T
authors.lastname: Li
authors.affiliation: Department of Crop, Soil and Environmental Sciences, Auburn University, Auburn, AL, 36849, USA.
authors.forename: Yucheng
authors.initials: Y
authors.lastname: Feng
authors.affiliation: Department of Entomology and Plant Pathology, Auburn University, Auburn, AL, 36849, USA. liunann@auburn.edu.
authors.forename: Nannan
authors.initials: N
authors.lastname: Liu
mesh_terms: D000818:Animals; D003465:Culex / Q000187:drug effects* / Q000235:genetics* / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics* / Q000378:metabolism; D000072472:Cytochrome P450 Family 6 / Q000235:genetics* / Q000378:metabolism; D004789:Enzyme Activation; D019476:Insect Proteins / Q000235:genetics / Q000378:metabolism; D007305:Insecticide Resistance / Q000235:genetics*; D007306:Insecticides / Q000494:pharmacology*; D009251:NADPH-Ferrihemoprotein Reductase / Q000235:genetics / Q000378:metabolism; D026023:Permethrin / Q000494:pharmacology*
chemical_list: D019476:Insect Proteins; D007306:Insecticides; D026023:Permethrin; D003577:Cytochrome P-450 Enzyme System; D000072472:Cytochrome P450 Family 6; D009251:NADPH-Ferrihemoprotein Reductase