UC Davis

Pyrethroid resistance in the mosquito, Aedes aegypti, is an issue for control professionals globally. Ae. aegypti is a global arbovirus pest, transmitting the viruses that cause dengue fever and yellow fever among others. Resistance is developed through mutations at the target-site (the voltage gated sodium channel) or through over expression or overactivation of detoxifying enzymes like cytochrome P450s. The overall contribution of different mechanisms in combination is relatively unknown, though the specific involvement of some mutations in the target site are well understood. Additionally, specific mechanisms differ geographically. Resistance is assessed through phenotypic and genotypic analysis. To begin to understand the general contributions of different resistance mechanisms to the resistance phenotype as well as to identify previously unknown genes that may be involved in detoxification, several experiments were carried out. First, to assess whether genotypic and phenotypic analysis of resistance show similar results, as well as to investigate the likelihood that other mechanisms are at play in California, we paired these two analyses on individual mosquitoes. We determined that there were significant differences in knockdown time in individuals with identical genotypes, indicating that other resistance mechanisms are present. Next, we employed a time-course RNA-seq analysis to investigate the role of detoxifying enzymes in pyrethroid response in a strain from California. Redox homeostasis related genes as well as lipid and carbohydrate metabolism related genes all corresponded to pyrethroid treatment. Additionally, heat shock proteins experienced significant upregulation across time, indicating a role for these in response. These results indicate an overall change in the redox and metabolic environment of female mosquitoes, spurring questions of whether these changes affect her eventual offspring. To explore whether pyrethroid treatment affects the ovarian transcriptome of mothers, we devised an experiment to assess transcriptomic changes in ovaries after exposure. We found 11 detoxification genes upregulated in the pyrethroid exposed group, included cytochrome P450s, glutathione synthetase, catalase, heat shock protein genes, and ABC transporters. In addition, we discovered shifts in genomic stability, mitochondrial function, and ribosome biogenesis. Overall, this indicates likely changes to the development rate of offspring. Further studies should focus on the association of changes to the ovarian transcriptome and the eventual resistance phenotype of the offspring. These results could indicate that insecticides are creating organisms better suited to live in a stressful environment, by mechanisms other than physical mutations.