Cytochrome P450s: Their Expression and Function in Insecticide Resistant Mosquitoes, Culex quinquefasciatus

Cytochrome P450-mediated detoxification is one of the most important mechanisms involved in insecticide resistance. With the availability of the whole genome sequence for the mosquito Culex quinquefasciatus, we are now able to characterize the expression profiles of P450s and their functions in insecticide resistant mosquitoes. In the current study, the expression profiles of a total of 204 P450 genes in both larvae and adults of Cx. quinquefasciatus are compared between susceptible (S-Lab) and resistant mosquito populations, two different field populations of mosquitoes (HAmCq and MAmCq), and field parental mosquitoes (HAmCq ^G0 and MAmCq^G0) and their permethrin selected offspring (HAmCq ^G8 and MAmCq^G6). The results provide direct evidence that multiple P450 genes are co-up-regulated in the genome of Cx. quinquefasciatus following permethrin selection. Among these up-regulated P450 genes, CYP6AA7 and CYP4C52v1 are up -regulated across the life stages and populations of mosquitoes, CYP9M10, CYP9J34, CYP9J45, CYP6P14 and CYP9AL1 are up-regulated in larvae of resistant mosquitoes across two different field populations, suggesting a link of these P450 genes with the permethrin selection in mosquito populations. The functional study using double-stranded RNA-mediated gene interference (RNAi) techniques reveals that silencing the expression of these up-regulated genes in mosquitoes results in a reduction of mosquitoes’ resistance. Furthermore, characterization of the transgenic lines of Drosophila melanogaster with the mosquito P450 genes shows an induction of the levels of tolerance to permethrin in these transgenic lines. Taken together, these results indicate that multiple up-regulated P450 genes are co-responsible for detoxification of insecticides and insecticide selection.