Roles of P450 genes in permethrin resistance of the house fly, Musca domestica

To characterize the P450 genes that play important roles in the pyrethroid resistance of house flies, 86 cytochrome P450 genes were selected, based on our whole transcriptome analysis of the house fly, to conduct the expression profile analysis in different house fly strains with different levels of permethrin resistance and autosome combinations. Our study showed that 4 P450 genes, CYP6A36, CYP6A52, CYP6D, and CYP4S24, were co-up-regulated in insecticide-resistant house flies compared to -susceptible house flies, and the expression of these genes was regulated by cis or trans regulatory factors/genes, which were mainly on autosomes 1, 2 and 5. Transgenic expression analysis of these four P450 genes in Drosophila melanogaster demonstrated that elevated expression of each of these 4 genes confers different levels of resistance to permethrin in the transgenic Drosophila, with relative lower level in CYP4S24 transgenic flies. Homology modeling and permethrin docking analysis further suggested potential abilities of all 4 P450 genes to metabolize permethrin, generating multiple metabolites except CYP4S24, which may have low degree metabolism of permethrin, consistent with lower level of resistance to permethrin in the CYP4S24 transgenic flies. Taken together, the study provides a global picture of P450 gene expression, regulation, autosomal interaction, and function in insecticide resistance of house flies.