'What I cannot create, I do not understand': functionally validated synergism of metabolic and target site insecticide resistance
'What I cannot create, I do not understand': functionally validated synergism of metabolic and target site insecticide resistance
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DOI：
10.1098/rspb.2020.0838
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发表时间：
2020-05-27
影响因子：
4.7
通讯作者：
Vontas, John
中科院分区：
文献类型：
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作者：
Samantsidis, George-Rafael;Panteleri, Rafaela;Vontas, John
昆虫对拟除虫菊酯耐药性的靶点突变和增强解毒作用的推定协同作用被假设为导致疟疾发病率和农作物产量显着后果的主要进化机制。结合遗传转化和CRISPR/Cas9基因组修饰，我们产生了在遗传背景中表达拟除虫菊酯代谢P450酶的转基因果蝇品系，沿着已知赋予靶位点抗性的电压门控钠通道（帕拉）中的工程突变。表达黄热病蚊子埃及伊蚊Cyp 9 J28同时也携带帕拉（V1016 G）突变的基因型显示出对溴氰菊酯的抗性比（RR）显著高于每种单独机制的产物（RR组合：19.85 > RRCyp 9 J28：1.77 x RRV 1016 G：3.00）。基因型表达A. aeneus花粉甲虫Cyp 6 BQ 23和也携带帕拉（L1014 F）（kdr）突变，显示几乎倍增的RR（RR组合：75.19 >= RRCyp 6 BQ 23：5.74 x RRL 1014 F：12.74）。拟除虫菊酯在靶位点的亲和力降低，延迟饱和，同时延长P450驱动解毒的持续时间，被认为是一种可能的潜在机制。靶位点和P450抗性基因座的组合可能是不利的，在田间种群中的杀虫剂选择的情况下，因为他们发挥一些健身不利的发展时间和繁殖力。从公共卫生和农业的杀虫剂抗药性管理角度来看，这些都是主要的考虑因素。
The putative synergistic action of target-site mutations and enhanced detoxification in pyrethroid resistance in insects has been hypothesized as a major evolutionary mechanism responsible for dramatic consequences in malaria incidence and crop production. Combining genetic transformation and CRISPR/Cas9 genome modification, we generated transgenic Drosophila lines expressing pyrethroid metabolizing P450 enzymes in a genetic background along with engineered mutations in the voltage-gated sodium channel (para) known to confer target-site resistance. Genotypes expressing the yellow fever mosquito Aedes aegypti Cyp9J28 while also bearing the para(V1016G) mutation displayed substantially greater resistance ratio (RR) against deltamethrin than the product of each individual mechanism (RRcombined: 19.85 > RRCyp9J28: 1.77 x RRV1016G: 3.00). Genotypes expressing Brassicogethes aeneus pollen beetle Cyp6BQ23 and also bearing the para(L1014F) (kdr) mutation, displayed an almost multiplicative RR (RRcombined: 75.19 >= RRCyp6BQ23: 5.74 x RRL1014F: 12.74). Reduced pyrethroid affinity at the target site, delaying saturation while simultaneously extending the duration of P450-driven detoxification, is proposed as a possible underlying mechanism. Combinations of target site and P450 resistance loci might be unfavourable in field populations in the absence of insecticide selection, as they exert some fitness disadvantage in development time and fecundity. These are major considerations from the insecticide resistance management viewpoint in both public health and agriculture.