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

描述(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丝虫寄生虫Wuchereria bancrofti给数亿人。抑制病媒-人类接触的方法，特别是与其他现有的病媒控制计划相结合，可能在控制这些疾病的传播方面发挥关键作用。与大多数其他食血昆虫一样，雌性蚊子主要通过呼出气体中的二氧化碳等嗅觉线索以及皮肤散发的其他气味来识别人类宿主。这项研究的目标是使用廉价且对环境安全的气味分子来改变伊蚊和库蚊的气味引导寻找宿主的行为，这些气味分子可以非常少量地用作有效的诱捕剂、掩蔽剂和驱蚊剂。为了实现这些目标，我们将重点研究二氧化碳感应神经元的功能分析。使用由味觉受体家族的三个成员组成的受体在这个神经元中检测到二氧化碳，味觉受体家族编码一个高度保守的异构体二氧化碳受体。我们计划使用神经生理学、化学信息学、分子、遗传学和行为学方法的综合平台：1)寻找有效的二氧化碳受体挥发性激动剂和拮抗剂，2)测试这些分子对雌性伊蚊和库蚊行为的影响，特别是拮抗剂在掩蔽剂或驱避剂中的能力，以及3)激动剂，以提高诱捕效率。在初步研究中，我们已经在伊蚊和库蚊中发现了一些二氧化碳受体的挥发性抑制物和激活剂。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，以抑制或激活雌性蚊子对二氧化碳的生理和行为反应。拟议研究的成功完成将导致开发新一代有效和安全的驱虫剂和引诱剂，这些驱虫剂和诱饵通过改变二氧化碳受体功能发挥作用。 公共卫生相关性：伊蚊和库蚊传播包括登革热和淋巴丝虫病在内的几种疾病，据估计，全世界有超过1亿人受到感染。蚊子通过嗅觉找到它们的人类宿主。这项拟议研究的目标是使用廉价且对环境安全的气味分子来改变伊蚊和库蚊的气味引导宿主寻找行为，这些气味分子可以非常少量地用作有效的诱捕剂、掩蔽剂和驱蚊剂。拟议研究的成功完成将导致开发新一代有效和安全的驱虫剂和引诱剂，这些驱虫剂和诱饵通过改变气味感受器功能发挥作用。

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.