Abstract
BackgroundMosquito resistance to the pyrethroid insecticides used to treat bednets threatens the sustainability of malaria control in sub-Saharan Africa. While the impact of target site insensitivity alleles is being widely discussed the implications of insecticide detoxification – though equally important – remains elusive. The successful development of new tools for malaria intervention and management requires a comprehensive understanding of insecticide resistance, including metabolic resistance mechanisms. Although three enzyme families (cytochrome P450s, glutathione S-transferases and carboxylesterases) have been widely associated with insecticide detoxification the role of individual enzymes is largely unknown.ResultsHere, constitutive expression patterns of genes putatively involved in conferring pyrethroid resistance was investigated in a recently colonised pyrethroid resistant Anopheles gambiae strain from Odumasy, Southern Ghana. RNA from the resistant strain and a standard laboratory susceptible strain, of both sexes was extracted, reverse transcribed and labelled with either Cy3- or Cy5-dye. Labelled cDNA was co-hybridised to the detox chip, a custom-made microarray containing over 230 A. gambiae gene fragments predominantly from enzyme families associated with insecticide resistance. After hybridisation, Cy3- and Cy5-signal intensities were measured and compared gene by gene. In both females and males of the resistant strain the cytochrome P450s CYP6Z2 and CYP6M2 are highly over-expressed along with a member of the superoxide dismutase (SOD) gene family.ConclusionThese genes differ from those found up-regulated in East African strains of pyrethroid resistant A. gambiae and constitute a novel set of candidate genes implicated in insecticide detoxification. These data suggest that metabolic resistance may have multiple origins in A. gambiae, which has strong implications for the management of resistance.
Highlights
Mosquito resistance to the pyrethroid insecticides used to treat bednets threatens the sustainability of malaria control in sub-Saharan Africa
Metabolic resistance is generally associated with three enzyme families: cytochrome P450 monooxygenases (P450s), carboxylesterases (COEs), and glutathione-Stransferases (GSTs) [10]
Gene expression associated with resistance status The expression levels of genes putatively involved in insecticide resistance were compared by co-hybridising labelled RNA from the pyrethroid resistant Odumasy strain and the standard susceptible Kisumu strain to a custom made microarray [16]. As both sexes of the resistant Odumasy strain showed high resistance to permethrin hybridisations were performed for both females and males
Summary
Mosquito resistance to the pyrethroid insecticides used to treat bednets threatens the sustainability of malaria control in sub-Saharan Africa. Three enzyme families (cytochrome P450s, glutathione S-transferases and carboxylesterases) have been widely associated with insecticide detoxification the role of individual enzymes is largely unknown. Two mechanisms of insecticide resistance play an important role in mosquitoes, target site insensitivity and meta-. Target site insensitivity to pyrethroids in Anopheles gambiae is associated with a single point mutation, commonly referred to as knock-down resistance (kdr). Metabolic resistance is generally associated with three enzyme families: cytochrome P450 monooxygenases (P450s), carboxylesterases (COEs), and glutathione-Stransferases (GSTs) [10]. Though the groups contain large numbers of genes, these enzyme families have multiple roles in the insect and only a small number are thought to be directly involved in insecticide metabolism. In addition to elevated expression of GSTE2, over-expression of two P450 genes, CYP6Z1 and CYP325A3, was observed in adult mosquitoes of the RSP strain [16,19]
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