Cytochrome P450s: Their expression and function in insecticide resistant mosquitoes, Culex quinquefasciatus

Cytochrome P450-mediated detoxification plays an important role in insecticide resistance. With the availability of the whole genome sequence of Culex quinquefasciatus, we are able to characterize the expression profiles of P450s and their functions in insecticide resistant mosquitoes. We currently compare the expression profiles of a total of 204 P450 genes in both larvae and adults of Cx. quinquefasciatus between susceptible (S-Lab) and resistant mosquitoes, two different field parental populations (HAmCq^G0 and MAmCq^G0), and permethrin selected highly resistant populations (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 field populations, suggesting a link of these P450 genes with the permethrin selection in mosquitoes. The functional study using double-stranded RNA-mediated gene interference (RNAi) techniques reveals that knockdown of individual or combination of these up-regulated genes in resistant mosquitoes results in a reduction of mosquitoes’ tolerance to permethrin, demonstrating that multiple up-regulated P450 genes are co-responsible for insecticide detoxification and insecticide resistance.