CRISPR/Cas9 modified An. gambiae carrying kdr mutation L1014F functionally validate its contribution in insecticide resistance and interaction with metabolic enzymes
CRISPR/Cas9 modified An. gambiae carrying kdr mutation L1014F functionally validate its contribution in insecticide resistance and interaction with metabolic enzymes
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CRISPR/Cas9 修饰 An。
DOI：
10.1101/2021.04.20.440595
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发表时间：
2021
期刊：
影响因子：
--
通讯作者：
Grigoraki L
中科院分区：
文献类型：
--
作者：
Grigoraki L
按蚊的抗药性是维持减少疟疾负担势头的主要障碍;减轻疟疾的战略需要更好地了解其内在机制。杀虫剂的靶位点突变（最广泛使用的拟除虫菊酯类的电压门控钠通道）和解毒酶的过度表达是常见的，但它们对表型抗性的相对贡献仍然知之甚少。在这里，我们提出了一个基因组编辑管道，在冈比亚按蚊中引入单核苷酸多态性，我们已经使用它来研究经典kdr突变L1014 F（基于冈比亚按蚊的L995 F）的影响，这是分布最广泛的耐药等位基因之一。在完全易感的遗传背景中引入1014 F，增加了对所有测试的拟除虫菊酯和滴滴涕的抗性水平，从氯菊酯的9.9倍到滴滴涕的24倍。引入1014 F等位基因足以降低暴露于溴氰菊酯处理的蚊帐后蚊子的死亡率，即使是目前唯一的抗性机制。当1014 F与谷胱甘肽转移酶Gste 2的过表达结合时，对氯菊酯的抗性增加，进一步证明了靶位点抗性和体内解毒酶之间的关键组合效应。我们还表明，携带1014 F等位基因纯合性的蚊子表现出健身的缺点，包括在幼虫阶段的死亡率增加和繁殖力和成年寿命的减少，这可能会产生后果的选择，将适用于该等位基因在该领域的强度。
Insecticide resistance inAnophelesmosquitoes is a major obstacle in maintaining the momentum in reducing the malaria burden; mitigating strategies require improved understanding of the underlying mechanisms. Mutations in the target site of insecticides (the voltage gated sodium channel for the most widely used pyrethroid class) and over-expression of detoxification enzymes are commonly reported, but their relative contribution to phenotypic resistance remain poorly understood. Here we present a genome editing pipeline to introduce single nucleotide polymorphisms inAn.gambiaewhich we have used to study the effect of the classical kdr mutation L1014F (L995F based onAn.gambiaenumbering), one of the most widely distributed resistance alleles. Introduction of 1014F in an otherwise fully susceptible genetic background increased levels of resistance to all tested pyrethroids and DDT ranging from 9.9-fold for permethrin to >24-fold for DDT. The introduction of the 1014F allele was sufficient to reduce mortality of mosquitoes after exposure to deltamethrin treated bednets, even as the only resistance mechanism present. When 1014F was combined with over-expression of glutathione transferase Gste2, resistance to permethrin increased further demonstrating the critical combined effect between target site resistance and detoxification enzymesin vivo. We also show that mosquitoes carrying the 1014F allele in homozygosity showed fitness disadvantages including increased mortality at the larval stage and a reduction in fecundity and adult longevity, which can have consequences for the strength of selection that will apply to this allele in the field.
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影响因子：
4.7
作者：
Hardstone, Melissa C.;Scott, Jeffrey G.
通讯作者：
Scott, Jeffrey G.
DOI：
10.1098/rspb.2020.0838
发表时间：
2020-05-27
影响因子：
4.7
作者：
Samantsidis, George-Rafael;Panteleri, Rafaela;Vontas, John
通讯作者：
Vontas, John
影响因子：
3.8
作者：
Rigby LM;Johnson BJ;Rašić G;Peatey CL;Hugo LE;Beebe NW;Hartel GF;Devine GJ
通讯作者：
Devine GJ
抗杀虫剂的适应性成本在喀麦隆Yaoundé市的Anopheles Coluzzii人口的生命特征上。
影响因子：
--
作者：
Nkahe DL;Kopya E;Djiappi-Tchamen B;Toussile W;Sonhafouo-Chiana N;Kekeunou S;Mimpfoundi R;Awono-Ambene P;Wondji CS;Antonio-Nkondjio C
通讯作者：
Antonio-Nkondjio C
影响因子：
3
作者：
Allossogbe M;Gnanguenon V;Yovogan B;Akinro B;Anagonou R;Agossa F;Houtoukpe A;Padonou GG;Akogbeto M
通讯作者：
Akogbeto M