Functional analysis of cytochrome P450 genes in the yellowfever mosquito Aedes aegypi (Diptera: Culicidae)

Cytochrome P450 monooxygenases (CYPs) belong to the superfamily of heme-thiolate proteins responsible for the metabolism of xenobiotic and endogenous compounds in various organisms. In insects, such as mosquitoes, CYPs along with others enzyme systems contribute to the rapid development of insecticide resistance that jeopardizes control strategies aimed at reducing vector borne illnesses among people. In this study we used RNA interference (RNAi)  followed by insecticide bioassay to reveal the role of five CYP transcripts including three individual genes (CYP6AA5, CYP6AL1, CYP9J32 ) and two splicing variants (CYP4J16A and CYP4J16B)  of CYP4J16 in the detoxification of three pyrethroid insecticides (permethrin,  cypermethrin and deltamethrin) in adults Aedes aegypti. Our results indicated that among the five transcripts, only silencing of CYP6AA5 increased the susceptibility of the mosquitoes exposed to cypermethrin compared to the controls. These results suggest that CYP6AA5 contributes to the detoxification of cypermethrin. Homology modeling of CYP6AA5 and insecticides docking analysis further suggest potential abilities of CYP6AA5 in metabolizing cypermethrin. Taken together, these results indicate that the role of CYPs in insecticide detoxification is both gene and insecticide specific. This information can help develop more effective strategies for insect pest management.