Glutathione-s-transferase mediated pyrethroid resistance in Culex pipiens s.l.

描述（由申请方提供）：拟除虫菊酯是用于控制尖音库蚊种群的主要杀虫剂。蚊子在美国和非洲。对拟除虫菊酯的抗药性正在这些蚊子的种群中出现，它们是美国西尼罗河病毒和非洲裂谷热病毒和班氏丝虫病的载体。直接证据有力地表明，这种抗性是由包括谷胱甘肽转移酶（GST）在内的酶促解毒介导的。因此，本研究的目标是分离那些负责介导抗性的GST同工酶，以开发用于诊断抗性状态的测定法。为实现上述目标，将努力实现以下目标：目标1。产生尖音库蚊复合蚊的单独的成虫和幼虫拟除虫菊酯抗性品系目标#2。纯化并获得将谷胱甘肽缀合至拟除虫菊酯的GST的氨基酸序列。使用细菌表达系统Aim#4克隆和表达GST同工酶。开发基于GST的拟除虫菊酯耐药性诊断检测方法一旦这些GST同工酶得到鉴定并开发了检测方法，它们就可用于耐药性监测、缓解和管理策略，以延长拟除虫菊酯的有效使用。这些研究还将有助于了解代谢抗性的机制，以帮助开发可能增强拟除虫菊酯的新一代杀虫剂和增效剂。

DESCRIPTION (provided by applicant): Pyrethroids are the major insecticides used to control populations of Culex pipiens s.l. mosquitoes in the USA and Africa. Resistance to pyrethroids is emerging in populations of these mosquitoes, where they are vectors of West Nile virus in the USA and Rift Valley fever virus and Bancroftian filariasis in Africa. Direct evidence strongly suggests that this resistance is mediated by enzymatic detoxification including Glutathione S Transferases (GSTs). The goal of this research is therefore to isolate those GST isozymes responsible for mediating resistance for the purpose of developing assays for diagnosing the status of resistance. To achieve the stated goal the following aims will be pursued; Aim #1. Generate separate adult and larval pyrethroid resistant strains of Culex pipiens complex mosquitoes Aim #2. Purify and obtain amino acid sequence of GSTs that conjugate glutathione to pyrethroids Aim #3. Clone and express GST isozymes using a bacterial expression system Aim #4. Develop GST based diagnostic assays for pyrethroid resistance Once these GST isozymes are identified and assays developed they can be used in resistance monitoring and mitigation and management strategies to prolong the effective use of pyrethroids. These studies will also lead to understanding the mechanism of metabolic resistance to aid in development of novel, next generation insecticides and synergists that may augment pyrethroids.