Department of Eco-Engineering, Guangdong Eco-Engineering Polytechnic, Guangzhou 510520, China; Department of Entomology, Michigan State University, East Lansing, MI 48824, USA.
Department of Entomology, Michigan State University, East Lansing, MI 48824, USA; Department of Applied Biology, College of Ecology and Environment, Kyungpook National University, Sangju, Republic of Korea.
Pestic Biochem Physiol. 2021 Jan;171:104727. doi: 10.1016/j.pestbp.2020.104727. Epub 2020 Oct 18.
Insecticide resistance is an ongoing challenge in agriculture and disease vector control. Here, we demonstrate a novel strategy to attenuate resistance. We used genomics tools to target fundamental energy-associated pathways and identified a potential "Achilles' heel" for resistance, a resistance-associated protein that, upon inhibition, results in a substantial loss in the resistance phenotype. Specifically, we compared the gene expression profiles and structural variations of the insulin/insulin-like growth factor signaling (IIS) pathway genes in DDT-susceptible (91-C) and -resistant (91-R) Drosophila melanogaster (Drosophila) strains. A total of eight and seven IIS transcripts were up- and down-regulated, respectively, in 91-R compared to 91-C. A total of 114 nonsynonymous mutations were observed between 91-C and 91-R, of which 51.8% were fixed. Among the differentially expressed transcripts, phosphoenolpyruvate carboxykinase (PEPCK), down-regulated in 91-R, encoded the greatest number of amino acid changes, prompting us to perform PEPCK inhibitor-pesticide exposure bioassays. The inhibitor of PEPCK, hydrazine sulfate, resulted in a 161- to 218-fold decrease in the DDT resistance phenotype (91-R) and more than a 4- to 5-fold increase in susceptibility in 91-C. A second target protein, Glycogen synthase kinase 3β (GSK3β-PO), had one amino acid difference between 91-C and 91-R, and the corresponding transcript was also down-regulated in 91-R. A GSK3β-PO inhibitor, lithium chloride, likewise reduced the resistance but to a lesser extent than did hydrazine sulfate for PEPCK. We demonstrate the potential role of IIS genes in DDT resistance and the potential discovery of an "Achilles' heel" against pesticide resistance in this pathway.
昆虫抗药性是农业和病媒控制中的一个持续挑战。在这里，我们展示了一种新的策略来减弱抗药性。我们使用基因组学工具靶向基本的能量相关途径，并确定了一个潜在的“阿喀琉斯之踵”，即一种与抗药性相关的蛋白质，当其受到抑制时，会导致抗药性表型的大量丧失。具体来说，我们比较了滴滴涕敏感（91-C）和抗滴滴涕（91-R）黑腹果蝇（果蝇）品系的胰岛素/胰岛素样生长因子信号（IIS）途径基因的基因表达谱和结构变异。与 91-C 相比，91-R 中共有 8 个和 7 个 IIS 转录本分别上调和下调。在 91-C 和 91-R 之间观察到 114 个非同义突变，其中 51.8%是固定的。在差异表达的转录本中，磷酸烯醇丙酮酸羧激酶（PEPCK）在 91-R 中下调，编码的氨基酸变化最多，促使我们进行 PEPCK 抑制剂-杀虫剂暴露生物测定。PEPCK 的抑制剂硫酸肼导致滴滴涕抗药性表型（91-R）降低 161-218 倍，而 91-C 的敏感性增加 4-5 倍以上。第二个靶蛋白糖原合酶激酶 3β（GSK3β-PO）在 91-C 和 91-R 之间有一个氨基酸差异，相应的转录本在 91-R 中也下调。GSK3β-PO 的抑制剂氯化锂同样降低了抗药性，但不如硫酸肼对 PEPCK 的影响大。我们证明了 IIS 基因在滴滴涕抗药性中的潜在作用，以及在该途径中发现抗药性的潜在“阿喀琉斯之踵”。
