Malaria continues to claim more than 400.000 lives every year, and represents one of the biggest health issues for humanity worldwide. Deltamethrin (DM) is one of the most potent insecticides used to eradicate malaria and belongs to type II pyrethroids. DM targets voltage-gated sodium channels (VGSCs) expressed in neuronal cells of target species. However, the off-target effects of chronic exposure to DM are poorly characterized. We use C. elegans as a non-target species, and the malaria vector Anopheles gambie, to identify molecular pathways that mediate insecticide toxicity and/or resistance to DM. Proteomic analysis of resistant mosquitoes compared to susceptible counterparts shows increased levels of OXPHOS and proteasomal proteins, and decreased levels of aminoacyl-tRNA biosynthesis and ribosomal proteins, suggesting reduction in protein translation. The proteomic profile of DM resistant mosquitoes resembles the profile of low insulin/IGF1 signaling (IIS) C. elegans mutants and indicates that resistant mosquitoes could experience low IIS. We tested the effects of DM on nematodes treated throughout their post-embryonic development. DM treated worms can develop to adulthood and produce viable progeny. We found that DM does not induce
sod-3 expression in wt animals, rather it attenuates
sod-3 induction in
daf-2 mutants and starved wt animals. In addition, DM significantly induces ER stress and antioxidant response in a dose dependent manner, while it alters the exploratory behavior of wild type worms in the presence of food. Our findings implicate IIS in deltamethrin-induced toxicity, in non-target species and in the development of mosquito resistance mechanisms. We are currently investigating whether modulation of IIS could serve as a putative toxicity and resistance management strategy.