You Chunmei, Zhang Lulu, Song Jiajia, Zhang Lei, Zhen Congai, Gao Xiwu
Department of Entomology, China Agricultural University, Beijing 100193, China.
Department of Entomology, China Agricultural University, Beijing 100193, China.
Int J Biol Macromol. 2023 May 1;236:123399. doi: 10.1016/j.ijbiomac.2023.123399. Epub 2023 Feb 11.
Long term and excessive insecticide use has resulted in some environmental problems and especially, insecticide resistance evolution in insect pests. The variation of cytochrome P450 monooxygenases (P450s), associated with the metabolic detoxification of toxic xenobiotics, is often involved in insecticide resistance. Here, we found that the variation in a P450 gene, CYP6G4, is the most important driver of carbamates resistance in the house fly (Musca domestica). Deciphering the detailed molecular mechanisms of the insecticide resistance is critical for performing suitable insecticide resistance management strategies. Our research results revealed that the combination of amino acid mutations (110C-330E-360N/S, 110C-330E-360S) of CYP6G4 could improve the resistance to propoxur. The nucleotide variations in the promoter region of CYP6G4 significantly increased the luciferase activity by the reporter gene assays. Additionally, miR-281-1-5p was confirmed to post-transcriptionally down-regulate the expression of CYP6G4. These findings suggest that three independent mechanisms; amino acid mutations of the P450 protein, mutations in the promoter region and low expression of post-trans-regulatory factors, as the powerful strategies for the insect resistance to toxic compounds, play a crucial role in the evolutionary processes of insecticide resistance.
长期且过量使用杀虫剂已导致一些环境问题，尤其是害虫对杀虫剂产生抗性。细胞色素P450单加氧酶（P450s）的变异与有毒异生物质的代谢解毒有关，常参与杀虫剂抗性的产生。在此，我们发现P450基因CYP6G4的变异是家蝇（Musca domestica）对氨基甲酸酯类杀虫剂产生抗性的最重要驱动因素。解析杀虫剂抗性的详细分子机制对于实施合适的杀虫剂抗性管理策略至关重要。我们的研究结果表明，CYP6G4的氨基酸突变组合（110C - 330E - 360N/S、110C - 330E - 360S）可提高对残杀威的抗性。通过报告基因检测，CYP6G4启动子区域的核苷酸变异显著增加了荧光素酶活性。此外，已证实miR - 281 - 1 - 5p在转录后下调CYP6G4的表达。这些发现表明，三种独立机制，即P450蛋白的氨基酸突变、启动子区域的突变以及转录后调控因子的低表达，作为昆虫对有毒化合物产生抗性的有力策略，在杀虫剂抗性的进化过程中起着关键作用。
