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Transcriptomic analysis of insecticide resistance in the lymphatic filariasis vector Culex quinquefasciatus.
Scientific Reports ( IF 3.8 ) Pub Date : 2019-08-06 , DOI: 10.1038/s41598-019-47850-w Walter Fabricio Silva Martins 1, 2 , Craig Stephen Wilding 1, 3 , Alison Taylor Isaacs 1 , Emily Joy Rippon 1 , Karine Megy 4, 5 , Martin James Donnelly 1, 6
Scientific Reports ( IF 3.8 ) Pub Date : 2019-08-06 , DOI: 10.1038/s41598-019-47850-w Walter Fabricio Silva Martins 1, 2 , Craig Stephen Wilding 1, 3 , Alison Taylor Isaacs 1 , Emily Joy Rippon 1 , Karine Megy 4, 5 , Martin James Donnelly 1, 6
Affiliation
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Culex quinquefasciatus plays an important role in transmission of vector-borne diseases of public health importance, including lymphatic filariasis (LF), as well as many arboviral diseases. Currently, efforts to tackle C. quinquefasciatus vectored diseases are based on either mass drug administration (MDA) for LF, or insecticide-based interventions. Widespread and intensive insecticide usage has resulted in increased resistance in mosquito vectors, including C. quinquefasciatus. Herein, the transcriptome profile of Ugandan bendiocarb-resistant C. quinquefasciatus was explored to identify candidate genes associated with insecticide resistance. High levels of insecticide resistance were observed for five out of six insecticides tested, with the lowest mortality (0.97%) reported to permethrin, while for DDT, lambdacyhalothrin, bendiocarb and deltamethrin the mortality rate ranged from 1.63-3.29%. Resistance to bendiocarb in exposed mosquitoes was marked, with 2.04% mortality following 1 h exposure and 58.02% after 4 h. Genotyping of the G119S Ace-1 target site mutation detected a highly significant association (p < 0.0001; OR = 25) between resistance and Ace1-119S. However, synergist assays using the P450 inhibitor PBO, or the esterase inhibitor TPP resulted in markedly increased mortality (to ≈80%), suggesting a role of metabolic resistance in the resistance phenotype. Using a novel, custom 60 K whole-transcriptome microarray 16 genes significantly overexpressed in resistant mosquitoes were detected, with the P450 Cyp6z18 showing the highest differential gene expression (>8-fold increase vs unexposed controls). These results provide evidence that bendiocarb resistance in Ugandan C. quinquefasciatus is mediated by both target-site mechanisms and over-expression of detoxification enzymes.
中文翻译：
淋巴丝虫病载体库克斯库克斯库克斯（Culex quinquefasciatus）对杀虫剂抗药性的转录组学分析。
昆克库蚊在传播具有公共卫生重要性的媒介传播疾病中起重要作用，包括淋巴丝虫病（LF）以及许多虫媒病毒疾病。当前，解决基于西洋参的媒介疾病的努力基于LF的大规模药物管理（MDA）或基于杀虫剂的干预。广泛和大量使用杀虫剂已导致蚊媒（包括昆卡梭菌）的抗药性增加。在此，对乌干达对苯达威威的抗药性昆西梭菌的转录组谱进行了研究，以鉴定与杀虫剂抗性相关的候选基因。在所测试的六种杀虫剂中，有五种观察到高水平的杀虫剂抗药性，据报道氯菊酯的死亡率最低（0.97％），而滴滴涕，lambacycyhalothrin，苯达威和溴氰菊酯的死亡率为1.63-3.29％。暴露的蚊子对苯达威的抗药性明显，暴露1小时后死亡率为2.04％，4小时后死亡率为58.02％。G119S Ace-1目标位点突变的基因分型检测到耐药性与Ace1-119S之间存在高度显着的关联（p <0.0001； OR = 25）。但是，使用P450抑制剂PBO或酯酶抑制剂TPP进行的协同测定导致死亡率显着增加（至≈80％），这表明代谢抗性在抗性表型中的作用。使用新颖的，定制的60 K全转录组微阵列，检测到了在抗性蚊子中明显过量表达的16个基因，其中P450 Cyp6z18显示出最高的差异基因表达（与未暴露的对照相比增加了8倍）。
更新日期：2019-08-06
中文翻译：
淋巴丝虫病载体库克斯库克斯库克斯（Culex quinquefasciatus）对杀虫剂抗药性的转录组学分析。
昆克库蚊在传播具有公共卫生重要性的媒介传播疾病中起重要作用，包括淋巴丝虫病（LF）以及许多虫媒病毒疾病。当前，解决基于西洋参的媒介疾病的努力基于LF的大规模药物管理（MDA）或基于杀虫剂的干预。广泛和大量使用杀虫剂已导致蚊媒（包括昆卡梭菌）的抗药性增加。在此，对乌干达对苯达威威的抗药性昆西梭菌的转录组谱进行了研究，以鉴定与杀虫剂抗性相关的候选基因。在所测试的六种杀虫剂中，有五种观察到高水平的杀虫剂抗药性，据报道氯菊酯的死亡率最低（0.97％），而滴滴涕，lambacycyhalothrin，苯达威和溴氰菊酯的死亡率为1.63-3.29％。暴露的蚊子对苯达威的抗药性明显，暴露1小时后死亡率为2.04％，4小时后死亡率为58.02％。G119S Ace-1目标位点突变的基因分型检测到耐药性与Ace1-119S之间存在高度显着的关联（p <0.0001； OR = 25）。但是，使用P450抑制剂PBO或酯酶抑制剂TPP进行的协同测定导致死亡率显着增加（至≈80％），这表明代谢抗性在抗性表型中的作用。使用新颖的，定制的60 K全转录组微阵列，检测到了在抗性蚊子中明显过量表达的16个基因，其中P450 Cyp6z18显示出最高的差异基因表达（与未暴露的对照相比增加了8倍）。
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