The role of gene splicing, gene amplification and regulation in mosquito insecticide resistance
The role of gene splicing, gene amplification and regulation in mosquito insecticide resistance
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DOI：
10.1098/rstb.1998.0320
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发表时间：
1998-10-29
期刊：
影响因子：
--
通讯作者：
Ranson, H
中科院分区：
文献类型：
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作者：
Hemingway, J;Hawkes, N;Ranson, H
在所有昆虫中，抗药性的主要途径是杀虫剂靶点的改变或杀虫剂解毒速度的改变。谷胱甘肽S转移酶、酯酶和单加氧酶三种酶系统参与了四大类杀虫剂的解毒作用。这些酶的作用方式是迅速将杀虫剂代谢成无毒产品，或快速结合并非常缓慢地翻转杀虫剂(隔离)。在库蚊中，最常见的有机磷抗药性机制是由两种酯酶的共同扩增引起的。扩增的酯酶是差异调节的，产生的Estβ2(1)比Est Alpha 2(1)多三倍。与这些酯酶相关的顺式作用调控序列正在研究中。在不同种库蚊中，所有扩增的酯酶都通过隔离起作用。在对杀虫剂敏感的昆虫中，它们与杀虫剂结合的速度比它们的非扩增对应物更快。相反，在按蚊中，基于酯酶的有机磷抗性总是基于底物特性的变化和一小部分杀虫剂的周转率增加。在抗药性蚊子中，谷胱甘肽S转移酶和单加氧酶的上调都是由于每个病例的单个主基因的影响。这些主要基因的产物上调了一系列酶的表达。蚊虫产生的谷胱甘肽S转移酶基因的不同5‘端和3’端的拼接增加了该酶家族的多样性。导致单加氧酶和谷胱甘肽S转移酶上调的反式作用调节因子仍然需要确定，但最近冈比亚按蚊定位克隆的分子工具的发展使这一点成为可能。
The primary routes of insecticide resistance in all insects are alterations in the insecticide target sites or changes in the rate at which the insecticide is detoxified. Three enzyme systems, glutathione S-transferases, esterases and monooxygenases, are involved in the detoxification of the four major insecticide classes. These enzymes act by rapidly metabolizing the insecticide to non-toxic products, or by rapidly binding and very slowly turning over the insecticide (sequestration). In Culex mosquitoes, the most common organophosphate insecticide resistance mechanism is caused by co-amplification of two esterases. The amplified esterases are differentially regulated, with three times more Est beta 2(1) being produced than Est alpha 2(1). Cis-acting regulatory sequences associated with these esterases are under investigation. All the amplified esterases in different Culex species act through sequestration. The rates at which they bind with insecticides are more rapid than those for their non-amplified counterparts in the insecticide-susceptible insects. In contrast, esterase-based organophosphate resistance in Anopheles is invariably based on changes in substrate specificities and increased turnover rates of a small subset of insecticides. The up-regulation of both glutathione S-transferases and monooxygenases in resistant mosquitoes is due to the effects of a single major gene in each case. The products of these major genes upregulate a broad range of enzymes. The diversity of glutathione S-transferases produced by Anopheles mosquitoes is increased by the splicing of different 5' ends of genes, with a single 3' end, within one class of this enzyme family. The trans-acting regulatory factors responsible for the up-regulation of both the monooxygenase and glutathione S-transferases still need to be identified, but the recent development of molecular tools for positional cloning in Anopheles gambiae now makes this possible.