title: Field-caught permethrin-resistant Anopheles gambiae overexpress CYP6P3, a P450 that metabolises pyrethroids.
abstract: Insects exposed to pesticides undergo strong natural selection and have developed various adaptive mechanisms to survive. Resistance to pyrethroid insecticides in the malaria vector Anopheles gambiae is receiving increasing attention because it threatens the sustainability of malaria vector control programs in sub-Saharan Africa. An understanding of the molecular mechanisms conferring pyrethroid resistance gives insight into the processes of evolution of adaptive traits and facilitates the development of simple monitoring tools and novel strategies to restore the efficacy of insecticides. For this purpose, it is essential to understand which mechanisms are important in wild mosquitoes. Here, our aim was to identify enzymes that may be important in metabolic resistance to pyrethroids by measuring gene expression for over 250 genes potentially involved in metabolic resistance in phenotyped individuals from a highly resistant, wild A. gambiae population from Ghana. A cytochrome P450, CYP6P3, was significantly overexpressed in the survivors, and we show that the translated enzyme metabolises both alpha-cyano and non-alpha-cyano pyrethroids. This is the first study to demonstrate the capacity of a P450 identified in wild A. gambiae to metabolise insecticides. The findings add to the understanding of the genetic basis of insecticide resistance in wild mosquito populations.
authors.affiliation: Liverpool School of Tropical Medicine, Liverpool, United Kingdom. pie.muller@liv.ac.uk
authors.forename: Pie
authors.initials: P
authors.lastname: Müller
authors.forename: Emma
authors.initials: E
authors.lastname: Warr
authors.forename: Bradley J
authors.initials: BJ
authors.lastname: Stevenson
authors.forename: Patricia M
authors.initials: PM
authors.lastname: Pignatelli
authors.forename: John C
authors.initials: JC
authors.lastname: Morgan
authors.forename: Andrew
authors.initials: A
authors.lastname: Steven
authors.forename: Alexander E
authors.initials: AE
authors.lastname: Yawson
authors.forename: Sara N
authors.initials: SN
authors.lastname: Mitchell
authors.forename: Hilary
authors.initials: H
authors.lastname: Ranson
authors.forename: Janet
authors.initials: J
authors.lastname: Hemingway
authors.forename: Mark J I
authors.initials: MJ
authors.lastname: Paine
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Donnelly
mesh_terms: D000818:Animals; D000852:Anopheles / Q000187:drug effects / Q000201:enzymology* / Q000235:genetics; D003001:Cloning, Molecular; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism*; D004926:Escherichia coli / Q000378:metabolism; D005838:Genotype; D019476:Insect Proteins / Q000235:genetics / Q000378:metabolism*; D007305:Insecticide Resistance / Q000235:genetics; D007306:Insecticides / Q000378:metabolism* / Q000494:pharmacology; D026023:Permethrin / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D019476:Insect Proteins; D007306:Insecticides; D026023:Permethrin; D003577:Cytochrome P-450 Enzyme System