Abstract：
Pyrethroids are widely used against agricultural pests and human disease vectors due to their broad insecticidal spectrum, fast action, and low mammalian toxicity. Unfortunately, overuse of pyrethroids has led to knockdown resistance (kdr) caused by mutations in voltage-gated sodium channels. Mutation I1011M was repeatedly detected in numerous pyrethroid-resistant Aedes aegypti populations from Latin American and Brazil. In addition, mutation G923V was first reported to coexist with I1011M in permethrin/DDT-resistant Ae. aegypti, whether G923V enhances the I1011M-mediated pyrethroid resistance in sodium channels remains unclear. In this study, we introduced mutations G923V and I1011M alone or in combination into the pyrethroid-sensitive sodium channel AaNav1-1 and examined the effects of these mutations on gating properties and pyrethroid sensitivity. We found mutations I1011M and G923V + I1011M shifted the voltage dependence of activation in the depolarizing direction, and none of mutations affect the voltage-dependence of inactivation. G923V and G923V + I1011M mutations reduced the channel sensitivity to both Type I and Type II pyrethroids. However, I1011M alone conferred resistance to Type I pyrethroids, not to Type II pyrethroids. Interestingly, significant synergism effects on Type I pyrethroids were observed between mutations G923V and I1011M. The effects of all mutations on channel sensitivity to DDT were identical with those to Type I pyrethroids. Our results confirm the molecular basis of resistance mediated by mutations G923V and I1011M and may contribute to develop molecular markers for monitoring pest resistance to pyrethroids.
摘要：
拟除虫菊酯由于其广泛的杀虫谱而广泛用于防治农业害虫和人类疾病媒介，快速行动,和低哺乳动物毒性。不幸的是,过度使用拟除虫菊酯会导致电压门控钠通道突变引起的敲减抗性（kdr）。在来自拉丁美洲和巴西的许多耐拟除虫菊酯埃及伊蚊种群中反复检测到I1011M突变。此外,首次报道突变G923V与氯菊酯/DDT抗性Ae中的I1011M共存。埃及伊蚊,G923V是否能增强I1011M介导的拟除虫菊酯对钠通道的耐药性尚不清楚.在这项研究中,我们将突变G923V和I1011M单独或联合引入拟除虫菊酯敏感性钠通道AaNav1-1,并检查了这些突变对门控特性和拟除虫菊酯敏感性的影响.我们发现突变I1011M和G923V+I1011M在去极化方向上改变了激活的电压依赖性,并且没有突变影响失活的电压依赖性。G923V和G923V+I1011M突变降低了通道对I型和II型拟除虫菊酯的敏感性。然而,I1011M单独赋予对I型拟除虫菊酯的抗性，不是II型拟除虫菊酯。有趣的是,在突变G923V和I1011M之间观察到对I型拟除虫菊酯的显着协同作用。所有突变对DDT通道敏感性的影响与I型拟除虫菊酯相同。我们的结果证实了由突变G923V和I1011M介导的抗性的分子基础，并可能有助于开发用于监测害虫对拟除虫菊酯抗性的分子标记。
