A potential role for 4g family cytochrome P450s in conferring insecticide resistance in mosquitoes by altering cuticle structure

The Anopheles gambiaecytochrome P450s CYP4G17 and CYP4G16 are the closest ortholog and paralog respectively, of the Drosophila melanogaster CYP4G1, the specific insect P450 with decarbonylase function that is involved in hydrocarbon biosynthesis.  The expression of both proteins is significantly higher in the oenocytes of insecticide resistance mosquitoes, compared to susceptible. Immunohistochemical stainings and western analysis showed that the CYP4G16 (including its different isoforms) and CYP4G17 proteins are found in the head and the carcass of the abdomen and are highly expressed in oenocytes, but not the midgut or malpighiam tubules, where  P450 detoxification genes have been localized previously.

Both proteins have been functionally co-expressed with their putative electron donor, cytochrome P450 reductase, in E coli using a fusion recombinant system, in order to determine precise catalytic activities (decarbonylase function; substrate specificity).

Hydrocarbon composition is being analysed in insecticide resistant and susceptible mosquito strains, and following CYP4G17 and CYP4G16 depletion (RNAi), using GCMS – based approaches. This data points to a potential role of cyp4 P450’s in insecticide resistance, via enhanced cuticular hydrocarbon biosynthesis.