Functional genetic validation of key genes conferring insecticide resistance in the major African malaria vector, Anopheles gambiae
Functional genetic validation of key genes conferring insecticide resistance in the major African malaria vector, Anopheles gambiae
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对非洲主要疟疾媒介冈比亚按蚊赋予杀虫剂抗性的关键基因进行功能遗传验证
DOI：
10.1101/749457
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发表时间：
2019
期刊：
影响因子：
--
通讯作者：
Adolfi A
中科院分区：
文献类型：
--
作者：
Adolfi A
冈比亚按蚊对公共卫生杀虫剂的所有4个主要类别（拟除虫菊酯、氨基甲酸酯、有机氯和有机磷酸盐）的耐药性限制了非洲疟疾传播的有效控制。解毒酶表达的增加与杀虫剂抗性有关，但它们在An中的直接功能验证。冈比亚仍然缺乏。在这里，我们使用GAL 4/UAS系统进行转基因分析，以检查由3个基因Cyp 6 m2，Cyp 6p 3和Gste 2的表达增加所赋予的杀虫剂抗性表型-在resistantAn中最常发现上调。冈比亚。我们在一份报告中报告了证据。冈比亚的研究表明，有机磷和有机氯抗性是由广泛组织中GSTE 2的过表达所赋予的。拟除虫菊酯和氨基甲酸酯抗性由类似的Cyp 6p 3过表达赋予，Cyp 6 m2在相同组织中过表达时仅赋予拟除虫菊酯抗性。相反，这种Cyp 6 m2的过度表达增加了对有机磷马拉硫磷的敏感性，可能是由于转化为毒性更大的代谢物马拉硫磷。当Cyp 6基因过表达仅限于中肠或卵母细胞时，没有赋予抗性表型，表明这两种组织都不参与由候选P450介导的杀虫剂抗性。赋予抗性的基因的验证提供了指导控制策略的标记，并且观察到的Cyp 6 m2引起的负交叉抗性为克服拟除虫菊酯抗性的双杀虫剂策略提供了证据。这些转基因。冈比亚抗性品系正在被用来测试活性化合物在其开发早期的“破坏抗性”功效。
Resistance inAnopheles gambiaeto members of all 4 major classes (pyrethroids, carbamates, organochlorines, and organophosphates) of public health insecticides limits effective control of malaria transmission in Africa. Increase in expression of detoxifying enzymes has been associated with insecticide resistance, but their direct functional validation inAn. gambiaeis still lacking. Here, we perform transgenic analysis using the GAL4/UAS system to examine insecticide resistance phenotypes conferred by increased expression of the 3 genes—Cyp6m2,Cyp6p3, andGste2—most often found up-regulated in resistantAn. gambiae. We report evidence inAn. gambiaethat organophosphate and organochlorine resistance is conferred by overexpression of GSTE2 in a broad tissue profile. Pyrethroid and carbamate resistance is bestowed by similarCyp6p3overexpression, andCyp6m2confers only pyrethroid resistance when overexpressed in the same tissues. Conversely, suchCyp6m2overexpression increases susceptibility to the organophosphate malathion, presumably due to conversion to the more toxic metabolite, malaoxon. No resistant phenotypes are conferred when eitherCyp6gene overexpression is restricted to the midgut or oenocytes, indicating that neither tissue is involved in insecticide resistance mediated by the candidate P450s examined. Validation of genes conferring resistance provides markers to guide control strategies, and the observed negative cross-resistance due toCyp6m2gives credence to proposed dual-insecticide strategies to overcome pyrethroid resistance. These transgenicAn. gambiae-resistant lines are being used to test the “resistance-breaking” efficacy of active compounds early in their development.
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影响因子：
4.6
作者：
Yang J
通讯作者：
Yang J
DOI：
10.1016/0272-0590(84)90189-1
发表时间：
1984-01-01
期刊：
FUNDAMENTAL AND APPLIED TOXICOLOGY
影响因子：
--
作者：
COHEN, SD
通讯作者：
COHEN, SD
DOI：
10.1007/978-1-60327-019-9_1
发表时间：
2009-01-01
期刊：
Methods in molecular biology (Clifton, N.J.)
影响因子：
--
作者：
Ringrose, Leonie
通讯作者：
Ringrose, Leonie
影响因子：
2.2
作者：
Martin, T;Ochou, OG;Fournier, D
通讯作者：
Fournier, D
转录因子MAF-S调节疟疾载体Anopheles Gambiae中对杀虫剂的代谢抗性。
影响因子：
4.4
作者：
Ingham VA;Pignatelli P;Moore JD;Wagstaff S;Ranson H
通讯作者：
Ranson H