Shandong Institute of Parasitic Diseases, Shandong First Medical University & Shandong Academy of Medical Sciences, Jining, Shandong, P.R. China.
National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention, Key Laboratory of Parasite and Vector Biology, MOH, National Center for International Research on Tropical Diseases, WHO Collaborating Centre for Tropical Diseases, Shanghai, China.
PLoS Negl Trop Dis. 2021 Mar 25;15(3):e0009237. doi: 10.1371/journal.pntd.0009237. eCollection 2021 Mar.
Mosquito control based on chemical insecticides is considered as an important element of the current global strategies for the control of mosquito-borne diseases. Unfortunately, the development of insecticide resistance of important vector mosquito species jeopardizes the effectiveness of insecticide-based mosquito control. In contrast to target site resistance, other mechanisms are far from being fully understood. Global protein profiles among cypermethrin-resistant, propoxur-resistant, dimethyl-dichloro-vinyl-phosphate-resistant and susceptible strain of Culex pipiens pallens were obtained and proteomic differences were evaluated by using isobaric tags for relative and absolute quantification labeling coupled with liquid chromatography/tandem mass spectrometric analysis. A susceptible strain of Culex pipiens pallens showed elevated resistance levels after 25 generations of insecticide selection, through iTRAQ data analysis detected 2,502 proteins, of which 1,513 were differentially expressed in insecticide-selected strains compared to the susceptible strain. Finally, midgut differential protein expression profiles were analyzed, and 62 proteins were selected for verification of differential expression using iTRAQ and parallel reaction monitoring strategy, respectively. iTRAQ profiles of adaptation selection to three insecticide strains combined with midgut profiles revealed that multiple insecticide resistance mechanisms operate simultaneously in resistant insects of Culex pipiens pallens. Significant molecular resources were developed for Culex pipiens pallens, potential candidates were involved in metabolic resistance and reducing penetration or sequestering insecticide. Future research that is targeted towards RNA interference of the identified metabolic targets, such as cuticular proteins, cytochrome P450s, glutathione S-transferases and ribosomal proteins proteins and biological pathways (drug metabolism-cytochrome P450, metabolism of xenobiotics by cytochrome P450, oxidative phosphorylation, ribosome) could lay the foundation for a better understanding of the genetic basis of insecticide resistance in Culex pipiens pallens.
基于化学杀虫剂的蚊虫控制被认为是当前控制蚊媒疾病全球战略的重要组成部分。不幸的是，重要病媒蚊虫物种对杀虫剂的抗药性发展威胁到基于杀虫剂的蚊虫控制的有效性。与靶标部位抗性相比，其他机制远未得到充分理解。本研究获得了对氯氰菊酯抗性、丙溴磷抗性、二甲基二氯-乙烯基-磷酸酯抗性和敏感品系白纹伊蚊的全球蛋白质图谱，并通过使用等重标记相对和绝对定量标记结合液相色谱/串联质谱分析评估蛋白质组差异。经过 25 代杀虫剂选择，敏感品系白纹伊蚊表现出较高的抗性水平，通过 iTRAQ 数据分析检测到 2502 种蛋白质，其中 1513 种在杀虫剂选择株中与敏感株相比差异表达。最后，分析了中肠差异蛋白表达谱，分别使用 iTRAQ 和平行反应监测策略选择 62 种蛋白进行差异表达验证。结合中肠图谱分析，对三种杀虫剂抗性选择的 iTRAQ 图谱进行分析，结果表明，多种杀虫剂抗性机制在白纹伊蚊抗性昆虫中同时起作用。为白纹伊蚊提供了重要的分子资源，候选蛋白涉及代谢抗性和降低穿透或隔离杀虫剂。针对鉴定的代谢靶标如表皮蛋白、细胞色素 P450s、谷胱甘肽 S-转移酶和核糖体蛋白的 RNA 干扰的未来研究，可以为更好地理解白纹伊蚊对杀虫剂的遗传基础奠定基础，如细胞色素 P450 代谢、细胞色素 P450 代谢、氧化磷酸化、核糖体）。
