Resistance to chemical insecticides including pyrethroids, the main insecticide class used against mosquitoes, has re-kindled interest in the use of neonicotinoids. In this context, the present study aimed to characterize 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 after 30 generations of exposure to imidacloprid (Imida-R line). After thirty generations of selection, larvae of the Imida-R line showed an 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.

对化学杀虫剂（包括拟除虫菊酯）（对蚊子使用的主要杀虫剂）的抗性重新引起了人们对使用新烟碱的兴趣。在这种情况下，本研究旨在表征埃及伊蚊中新烟碱抵抗的分子基础。。通过结合从在吡虫啉（Imida-R系）暴露30代后在幼虫期选择的实验室菌株获得的转录组学和基因组数据，研究了抗药性机制。经过三十代的选择，Imida-R系的幼虫显示出对吡虫啉的抗性提高了8倍，并且对拟除虫菊酯菊酯和溴氰菊酯的交叉耐受性强。拟除虫菊酯的交叉抗性仅在幼虫先前接触吡虫啉时才在成年人中观察到，这表明在成年期抗性等位基因的表达较低但可诱导。Imida-R系的抗性与雌性幼虫发育时间较慢有关。与抗药性相关的幼虫中多种解毒酶过度转录，包括P450 CYP6BB2，CYP9M9CYP6M11和以前与拟除虫菊酯耐药性相关。其中一些连同其氧化还原伴侣NADPH P450还原酶也受到与抗性相关的非同义突变的影响。结合基因组和转录组数据，可以鉴定与CYP6BB2在耐药株中上调相关的启动子变异。总体而言，这些数据证实了P450在Ae的新烟碱抵抗中的关键作用。埃及斑潜蝇及其赋予拟除虫菊酯交叉耐药性的潜力，引起人们对新烟碱类在该蚊子中进行耐药性管理的关注。