Using metabolomic analysis to generate insights into pyrethroid metabolism and resistance in California Aedes aegypti

Resistance to pyrethroid based insecticides has facilitated the rapid spread of Aedes aegypti mosquitoes throughout California. Aedes aegypti demonstrate both metabolic and target site resistance mechanisms to insecticides, but precise mechanisms of pyrethroid detoxification are not yet well described and appear to vary between and within populations. For our study, we produced F2 generation colonies representing two genetically distint populations of Aedes aegypti from the San Joaquin Valley and from Southern California. These two populations were then subjected to a modified CDC bottle-assay with Deltamethrin, a pyrethroid insecticide. Following Deltamethrin exposure, we observed knock-down times and collected samples from the upper and lower knock-down quartiles, representing susceptible and resistant insects. We apportioned 10 pools of 5 adult female Aedes aegypti organized by population and susceptible or resistant and submitted them to the West Coast Metabolomics center for high-throughput metabolomic analysis. This technique offers a snapshot of the insects’ metabolomes, revealing different levels of activity and demands on metabolic pathways. We analyzed the data in Metaboanalyst to look for differences between the susceptible and resistant insects and shared features between the two study populations. These analyses revealed that the susceptible individuals from both populations had higher levels of biomarkers associated with oxidative stress. Further research could shed new light on how invasive California Aedes aegypti are detoxifying pyrethroids and ultimately allow for the discovery of better targeted vector control that exploits the mosquitoes’ metabolic vulnerabilities.