GSE174009
Molecular bases of P450-mediated resistance to the neonicotinoid insecticide imidacloprid in the mosquito Ae. aegypti
Resistance to chemical insecticides including pyrethroids, the main insecticide class used against mosquitoes, led to a regain of interest for neonicotinoids. In this context, the present study aims at characterizing the molecular basis of neonicotinoid resistance in the mosquito Aedes aegypti. Resistance mechanisms were studied by combining transcriptomic and genomic data obtained from a laboratory strain selected at the larval stage for 30 generations with imidacloprid (Imida-R line). After thirty generations of selection, larvae of Imida-R line showed a 8-fold increased resistance to imidacloprid and a significant cross-tolerance to the pyrethroids permethrin and deltamethrin. Cross-resistance to pyrethroids was only observed in adults when larvae were previously exposed to imidacloprid suggesting a low but inducible expression of resistance alleles at the adult stage. Resistance of the Imida-R line was associated with a slower larval development time in females. Multiple detoxification enzymes were over-transcribed in larvae in association with resistance including the P450s CYP6BB2, CYP9M9 and CYP6M11 previously associated with pyrethroid resistance. Some of them together with their redox partner NADPH P450 reductase were also affected by non-synonymous mutations associated with resistance. Combining genomic and transcriptomic data allowed identifying promoter variations associated with the up-regulation of CYP6BB2 in the resistant line. Overall, these data confirm the key role of P450s in neonicotinoid resistance in Ae. aegypti and their potential to confer cross-resistance to pyrethroids, raising concerns about the use of neonicotinoids for resistance management in this mosquito species. Overall design: mRNAseq  from Aedes aegypti  4th stage Larvae