Molecular Mechanism of Pyrethroid Repellency in Drosophila Melanogaster and Mosquitoes

 描述(申请人提供)：拟除虫菊酯是从菊花的花提取物中合成的天然除虫菊酯的类似物，以其杀虫活性和对哺乳动物的低毒而闻名。因此，它们被广泛用于控制许多节肢动物害虫，包括传播人类疾病的昆虫媒介。除虫菊酯的直接杀虫活性是基于它们结合和超激活昆虫神经系统电压门控钠通道的能力，值得注意的是，自然产生的拟除虫菊酯和挥发性拟除虫菊酯具有明显的空间排斥作用。事实上，空间上的 目前正在对这些化合物的驱避性进行评估，以控制人类疾病媒介。然而，拟除虫菊酯空间驱避性的分子基础仍然难以捉摸。这项工作的中心假设是，拟除虫菊酯和挥发性拟除虫菊酯通过与特定的嗅觉受体相互作用而发挥其空间排斥作用，而不依赖于它们基于钠通道的杀虫活性。这一新建议的具体目的是：1)鉴定果蝇对拟除虫菊酯有反应的感受器和嗅觉受体(OR)。2)蚊虫对拟除虫菊酯敏感感受器和拟除虫菊酯感受器的鉴定。3)拟除虫菊酯反应ORs在空间排斥中的作用。将结合电生理学和分子遗传学方法来验证这一假设，最终目标是识别负责拟除虫菊酯空间排斥的嗅觉受体。这项拟议的研究在开始阐明昆虫媒介对除虫菊酯和拟除虫菊酯的驱避性的分子基础方面具有创新性和开创性。所获得的知识将为建立基于空间驱避性的替代昆虫媒介控制策略奠定基础，最终目标是提高拟除虫菊酯的效用，减少通过昆虫媒介传播疾病。

 DESCRIPTION (provided by applicant): Pyrethroids are synthetic analogues of naturally occurring pyrethrum from the flower extracts of Chrysanthemum and are best known for their insecticidal activity and low toxicity to mammals. As such, they are widely used in the control of numerous arthropod pests, including insect vectors that transmit human disease. Beside the direct insecticidal activity of pyrethroids which is based on their ability to bind and hyper- activate voltage-gated sodium channels in the insect nervous system, remarkably, natural-occurring pyrethrum and volatile pyrethroids exhibit clear spatial repellency. In fact, the spatial repellency of these compounds is now being evaluated for human disease vector control. However, the molecular basis of the spatial repellency of pyrethroid remains elusive. The central hypothesis of the proposed work is that pyrethrum and volatile pyrethroids exert their spatial repellency by interacting with specific olfactory receptors independent of their sodium channel-based insecticidal activity. The specific aims of this new proposal are: 1) Identification of pyrethroid-responsive sensilla and olfaction receptors (OR) in Drosophila melanogaster. 2) Identification of pyrethroid-responsive sensilla and ORs in mosquitoes. 3) Determination of the role of pyrethroid-responsive ORs in spatial repellency. A combination of electrophysiology and molecular genetic methods will be used to test the hypothesis, with the final goal of identificatio of olfactory receptors that are responsible for spatial repellency of pyrethroids. The proposed research is innovative and pioneering in beginning to elucidate the molecular basis of repellency of insect vectors to pyrethrum and pyrethroids. The knowledge gained will form the foundation on which to build alternative insect vector control strategies based on spatial repellency, with th ultimate goal of enhancing the utility of pyrethroids and reducing disease transmission by insect vectors.