Gene expression temporal analysis of pyrethroid response in Californian Aedes aegypti

Aedes aegypti, the vector of Zika and dengue, established in California in 2013 and have spread to 22 counties across the state. These mosquitoes arrived with resistance to pyrethroids, the primary class of insecticides used for public health applications. Pyrethroids act on the insect voltage gated sodium channels causing prolonged depolarization and death. Resistance is developed through mutations at the target site or over-expression of detoxifying enzymes like cytochrome P450s and glutathione-S-transferases (GSTs), however over 100 genes code for P450s in mosquitoes. To identify putative resistance mediating enzymes as well as the overall genetic response to insecticide exposure, mosquitoes were exposed to permethrin for 1 hour, then placed in a cage and collected 6, 10, and 24 hours post exposure for Tag-seq. The analysis identified 20 cytochrome P450s and 6 GSTs with significant increases in expression. Enzymes associated with oxidation-reduction reactions were overrepresented across time points suggesting the response results in significant oxidative stress. Another significant feature revealed upregulation of enzymes required for fundamental metabolic activities including glycolysis, the pentose phosphate shunt, and lipid metabolism. Overall, these findings reveal that these mosquitoes have a strong genetic response to insecticide exposure. In addition, this response appears to require activation of other fundamental metabolic pathways to reduce the associated oxidative stress and maintain the demand for energy generated by these activities. These results provide evidence of metabolic resistance in this population, new enzymatic targets for investigation, and new questions to pursue as to the resistance profile of these invasive Californian populations.