The transcription factor Maf-S regulates metabolic resistance to insecticides in the malaria vector Anopheles gambiae.

The transcription factor Maf-S regulates metabolic resistance to insecticides in the malaria vector Anopheles gambiae.
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转录因子MAF-S调节疟疾载体Anopheles Gambiae中对杀虫剂的代谢抗性。

DOI:
10.1186/s12864-017-4086-7
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发表时间:
2017-08-30
期刊:
影响因子:
4.4
通讯作者:
Ranson H
Ranson H
中科院分区:
生物学2区
文献类型:
--
作者:
Ingham VA;Pignatelli P;Moore JD;Wagstaff S;Ranson H

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非洲的疟疾控制依赖于杀虫剂的使用,但有限数量的化学品的密集使用导致蚊子种群产生抗药性。使杀虫剂解毒的酶的产生增加是最有效的抗性机制之一。几种代谢酶与杀虫剂抗性有关,但控制其表达的过程在很大程度上仍然难以捉摸。在这里,我们表明,转录因子Maf-S调节多种解毒基因的表达,包括关键的杀虫剂代谢CYP 6 M2和GSTD 1在非洲疟疾媒介冈比亚按蚊。通过RNAi诱导的敲低,这种转录因子的减弱降低了这些效应物的转录水平,并显着增加了暴露于拟除虫菊酯杀虫剂和DDT后的死亡率氯菊酯:9.2%至19.2%(p = 0.015),溴氰菊酯:3.9%至21.6%(p = 0.036)和滴滴涕:1%至11.7%(p = <0.01),同时显著降低有机磷马拉硫磷诱导的死亡率(79.6%至8.0%(p = <0.01))。还鉴定了Maf-S调控的其他基因,为该转录因子在昆虫中的作用提供了新的见解。 Maf-S是按蚊解毒基因的关键调节因子。破坏这种转录因子对蚊子对不同杀虫剂类别的反应具有相反的影响,这为拟除虫菊酯和有机磷酸酯之间报告的负交叉抗性提供了机制解释。本文的在线版本(10.1186/s12864-017-4086-7)包含补充材料,可供授权用户使用。
Malaria control in Africa is dependent upon the use insecticides but intensive use of a limited number of chemicals has led to resistance in mosquito populations. Increased production of enzymes that detoxify insecticides is one of the most potent resistance mechanisms. Several metabolic enzymes have been implicated in insecticide resistance but the processes controlling their expression have remained largely elusive. Here, we show that the transcription factor Maf-S regulates expression of multiple detoxification genes, including the key insecticide metabolisers CYP6M2 and GSTD1 in the African malaria vector Anopheles gambiae. Attenuation of this transcription factor through RNAi induced knockdown reduced transcript levels of these effectors and significantly increased mortality after exposure to the pyrethroid insecticides and DDT (permethrin: 9.2% to 19.2% (p = 0.015), deltamethrin: 3.9% to 21.6% (p = 0.036) and DDT: 1% to 11.7% (p = <0.01), whilst dramatically decreasing mortality induced by the organophosphate malathion (79.6% to 8.0% (p = <0.01)). Additional genes regulated by Maf-S were also identified providing new insight into the role of this transcription factor in insects. Maf-S is a key regulator of detoxification genes in Anopheles mosquitoes. Disrupting this transcription factor has opposing effects on the mosquito’s response to different insecticide classes providing a mechanistic explanation to the negative cross resistance that has been reported between pyrethroids and organophosphates. The online version of this article (10.1186/s12864-017-4086-7) contains supplementary material, which is available to authorized users.
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