Institution of Pesticide Science, College of Plant Protection, Northwest A&F University, Yangling, Shaanxi, 712100, China.
Key Laboratory of Botanical Pesticide R&D in Shaanxi Province, Yangling, Shaanxi, 712100, China.
Insect Sci. 2022 Jun;29(3):817-826. doi: 10.1111/1744-7917.12973. Epub 2021 Oct 25.
Voltage-gated sodium channels are the primary target of pyrethroid insecticides. Mutations in sodium channel confer knockdown resistance (kdr) to pyrethroids in various arthropod pests. Haedoxan A (HA) is the major insecticidal component from Phryma leptostachya. It has been shown that HA alters electrical responses at the Drosophila neuromuscular junction and modifies the gating properties of cockroach sodium channels expressed in Xenopus oocytes. However, whether sodium channel mutations that confer pyrethroid resistance also affect the action of HA is unknown. In this study, we conducted bioassays using HA and permethrin in two Drosophila melanogaster strains: w , an insecticide-susceptible strain, and para , a pyrethroid-resistant strain due to a I265N mutation in the sodium channel, and identified a new case of negative cross-resistance (NCR) between permethrin and HA. Both para larvae and adults were more resistant to permethrin, as expected. However, both para larvae and adults were more sensitive to HA compared to w . We confirmed that the I265N mutation reduced the sensitivity to permethrin of a Drosophila sodium channel variant, DmNa 22, expressed in Xenopus oocytes. Interestingly, the I265N mutation also abolished the effect of HA on sodium channels. Further characterization showed that I265 on the sodium channels is critical for the action of both pyrethroids and HA on sodium channels, pointing to an overlapping mode of action between pyrethroids and HA on the sodium channel. Overall, our results suggest an I265N-independnt mechanism(s) in para flies that is responsible for the NCR between permethrin and HA at the whole insect level.
电压门控钠离子通道是拟除虫菊酯杀虫剂的主要靶标。钠离子通道中的突变使各种节肢动物害虫对拟除虫菊酯产生击倒抗性（kdr）。黄莲素 A（HA）是黄莲的主要杀虫成分。已表明 HA 改变了果蝇神经肌肉接头的电反应，并修饰了在非洲爪蟾卵母细胞中表达的蟑螂钠离子通道的门控特性。然而，赋予拟除虫菊酯抗性的钠离子通道突变是否也会影响 HA 的作用尚不清楚。在这项研究中，我们使用 HA 和氯菊酯在两个黑腹果蝇品系中进行了生物测定：w，一种对杀虫剂敏感的品系，和 para，一种由于钠离子通道中的 I265N 突变而对拟除虫菊酯具有抗性的品系，并确定了氯菊酯和 HA 之间新的负交叉抗性（NCR）。正如预期的那样，para 幼虫和成虫对氯菊酯的抗性更强。然而，与 w 相比，para 幼虫和成虫对 HA 的敏感性更高。我们证实 I265N 突变降低了在非洲爪蟾卵母细胞中表达的果蝇钠离子通道变体 DmNa22 对氯菊酯的敏感性。有趣的是，I265N 突变也消除了 HA 对钠离子通道的作用。进一步的特征分析表明，钠离子通道上的 I265 对于拟除虫菊酯和 HA 对钠离子通道的作用都是至关重要的，这表明拟除虫菊酯和 HA 在钠离子通道上的作用模式有重叠。总的来说，我们的结果表明，para 果蝇中存在一种 I265N 独立的机制，负责在整个昆虫水平上氯菊酯和 HA 之间的 NCR。
