Overproduction of a P450 that metabolizes diazinon is linked to a loss-of-function in the chromosome 2 ali-esterase (MdαE7) gene in resistant houseflies
Overproduction of a P450 that metabolizes diazinon is linked to a loss-of-function in the chromosome 2 ali-esterase (MdαE7) gene in resistant houseflies
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DOI：
10.1046/j.0962-1075.2001.00303.x
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发表时间：
2001-12-01
影响因子：
2.6
通讯作者：
Feyereisen, R
中科院分区：
文献类型：
--
作者：
Sabourault, C;Guzov, VM;Feyereisen, R
家蝇抗药性菌株中解毒酶的上调是代谢抗性的常见机制。然而，这种杀虫剂代谢增加的分子基础尚不清楚。在多重耐药性罗格斯菌株中，几种细胞色素 P450 和谷胱甘肽 S-转移酶在转录水平上持续过度表达。过度表达是反式调节的结果，调节基因位于 2 号染色体上。α E7 酯酶基因中的 Gly137 到 Asp 点突变会导致羧酸酯酶活性丧失，与家蝇和羊绿蝇的有机磷抗性有关。我们在此表明，纯化的重组 CYP6A1 能够高效解毒二嗪农。我们还表明，α E7 酯酶基因中的 Gly137 到 Asp 点突变或该基因座的缺失会导致 CYP6A1 蛋白的抗性和过量产生。基于这些发现，我们提出，α E7 基因野生型 Gly137 等位基因的缺失释放了编码解毒酶（如 CYP6A1）的基因的转录抑制，从而导致对二嗪农的代谢抗性。
Up-regulation of detoxifying enzymes in insecticide-resistant strains of the house fly is a common mechanism for metabolic resistance. However, the molecular basis of this increased insecticide metabolism is not well understood. In the multiresistant Rutgers strain, several cytochromes P450 and glutathione S-transferases are constitutively overexpressed at the transcriptional level. Overexpression is the result of transregulation, and a regulatory gene has been located on chromosome 2. A Gly137 to Asp point mutation in alpha E7 esterase gene, leading to the loss of carboxylesterase activity, has been associated with organophosphate resistance in the house fly and the sheep blowfly. We show here that purified recombinant CYP6A1 is able to detoxify diazinon with a high efficiency. We also show that either the Gly137 to Asp point mutation In alpha E7 esterase gene or a deletion at this locus confer resistance and overproduction of the CYP6A1 protein. Based on these findings, we propose it is the absence of the wild-type Gly137 allele of the alpha E7 gene that releases the transcriptional repression of genes coding for detoxification enzymes such as CYP6A1, thereby leading to metabolic resistance to diazinon.