Disruption of Host-Seeking Behavior in Aedes and Culex Mosquitoes using Odorants

描述（由申请人提供）：埃及伊蚊传播登革热和黄热病病毒，致倦库蚊传播西尼罗河病毒和班氏乌切里氏丝虫病寄生虫给数亿人。抑制病媒与人接触的方法，特别是与其他现有的病媒控制方案相结合，可能在控制这些疾病的传播方面发挥关键作用。和大多数其他吸血昆虫一样，雌性蚊子主要通过嗅觉来识别它们的人类宿主，比如呼出的二氧化碳，以及皮肤散发出的其他气味。本研究的目的是利用廉价且环境安全的气味分子来改变伊蚊和库蚊的气味导向寻找宿主行为，这些分子可以作为有效的诱捕剂、掩蔽剂和驱蚊剂，少量使用。为了实现这些目标，我们将重点研究二氧化碳传感神经元的功能分析。在这个神经元中，二氧化碳是通过一个由味觉受体家族的三个成员组成的受体来检测的，这个受体编码一个高度保守的异源二氧化碳受体。我们计划利用神经生理学，化学信息学，分子，遗传和行为方法的综合平台；1)鉴定CO2受体的有效挥发性激动剂和拮抗剂；2)测试这些分子对雌伊蚊和库蚊行为的影响，特别是拮抗剂在掩蔽剂或驱蚊剂中的作用；3)激动剂提高捕获效率。在初步研究中，我们已经在伊蚊和库蚊中发现了几种挥发性CO2受体抑制剂和激活剂。我们现在建议进行进一步的研究，以确定更有效的化学物质，抑制或激活雌性蚊子对二氧化碳的生理和行为反应。这些研究的成功完成将导致新一代有效和安全的驱蚊剂和诱捕剂的开发，这些驱蚊剂和诱捕剂通过改变二氧化碳受体的功能起作用。

DESCRIPTION (provided by applicant): Aedes aegypti mosquitoes transmit Dengue and Yellow Fever virus, and Culex quinquefasciatus mosquitoes transmit the West Nile virus and filarial parasite Wuchereria bancrofti to hundreds of millions of people. Methods for inhibiting vector- human contact, particularly in conjunction with other existing programs of vector control, may play a critical role in controlling the spread of these diseases. Female mosquitoes, like most other blood-feeding insects, identify their human hosts primarily using olfactory cues like carbon dioxide in exhaled breath, as well as other odors present in skin emanations. The goal of this research is to modify odor-guided host-seeking behavior of Aedes and Culex mosquitoes using cheap and environmentally safe odor molecules that can be used in very small quantities as effective trapping agents, masking agents and repellents. To achieve these goals we will focus on functional analyses of the CO2 sensing neuron. CO2 is detected in this neuron using a receptor comprising three members of the Gustatory receptor family that encode a highly conserved heteromeric CO2 receptor. We plan to use an integrated platform of neurophysiology, chemical- informatics, molecular, genetic and behavioral methods to; 1) identify effective volatile agonists and antagonists for the CO2 receptors, 2) test the effects of these molecules on behavior of female Aedes and Culex mosquitoes, in particular, for the ability of antagonists in masking agents or repellents, and 3) agonists to improve trapping efficiency. In preliminary studies, we have identified a few volatile inhibitors and activators of the CO2 receptor in Aedes and Culex. We now propose to conduct further studies to identify more effective chemicals that inhibit or activate physiological and behavioral responses to CO2 in female mosquitoes. Successful completion of the proposed studies will lead to the development of a new generation of effective and safe insect repellents and lures that act by modifying CO2 receptor function. PUBLIC HEALTH RELEVANCE: Aedes and Culex mosquitoes transmit several diseases including Dengue and lymphatic filariasis, and it is estimated that there are more than a hundred million people worldwide that are infected. Mosquitoes find their human hosts using the sense of smell. The goal of the proposed research is to modify odor-guided host-seeking behavior of Aedes and Culex mosquitoes using cheap and environmentally safe odor molecules that can be used in very small quantities as effective trapping agents, masking agents and repellents. Successful completion of the proposed studies will lead to the development of a new generation of effective and safe insect repellents and lures that act by modifying odor receptor function.