The Effects of Chemical Repellents on Olfactory Receptors of the Aedes aegypti Mosquito in Response to Human Odorants – the Mechanism Underlying Host-seeking and Blood-feeding Behaviors

化学驱避剂对埃及伊蚊嗅觉受体响应人类气味的影响——寻找宿主和吸血行为的机制

• 批准号: 10525259
• 负责人: NANNAN LIU
• 金额: $ 7.48万
• 依托单位: AUBURN UNIVERSITY AT AUBURN
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-11-12 至 2023-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10525259
• 关键词: Acetylcholinesterase; Aedes; Affect; Behavior; Biological; Blood; Bypass; Central Africa; Cessation of life; Chemicals; Country; Culicidae; Cytochrome P450; Detection; Development; Disease; Disease Outbreaks; Electrodes; Exhibits; Exposure to; Feeding behaviors; Female; Food; Funding; Gene Expression; Gene Proteins; Goals; Human; Incidence; Industry; Insect Repellents; Insecta; Insecticide Resistance; Insecticides; Knock-in; Knock-out; Malaria; Measures; Molecular; Mosquito Control; Mosquito-borne infectious disease; Neurons; Odors; Olfactory Pathways; Olfactory Receptor Neurons; Pathway interactions; Population; Public Health; Reporting; Research; Resistance; Smell Perception; System; Techniques; Terpenes; Testing; Toxic effect; United States National Institutes of Health; Voltage-Clamp Technics; Xenopus oocyte; desensitization; feeding; knock-down; mosquito reproduction; olfactory receptor; prevent; pyrethroid; response; transmission process; vector mosquito

Project Summary/Abstract The long-term goal of the proposed research is to develop effective, alternative chemical repellents that counter mosquito host-seeking and blood-feeding behaviors by disrupting the mosquito’s human odor- detection mechanism. The information gained in this proposal will inform the development of chemical repellents that by-pass known mechanisms of insecticide resistance in order to reduce the incidence of mosquito-borne diseases and to protect public health. When seeking blood meals, mosquitoes rely on their olfactory system to detect chemical odorants emitted by their human hosts [8]; these human odorants assist in the t ransmission of mosquito-related diseases to humans. Using chemical repellents that disrupt the odor-detection mechanisms in mosquitoes may be a viable alternative strategy to current insecticides, such as DEET (Section A.3), for desensitizing the mosquito’s ability to smell humans. A better understanding is needed of the mechanisms governing the interactions among chemical repellents, host odorants, and the response of olfactory receptors of mosquitoes to enable the development of new repellent alternatives that will desensitize the mosquito to humans, thus interfering with the mosquito recognizing its human host. In preliminary studies, we investigated the interactions of 48 repellent chemicals with the olfactory receptor neurons (ORNs) of the Aedes aegypti mosquito, and identified several terpene/terpenoid compounds that exhibit inhibitory effects on mosquito ORNs [40]. We have further characterized the responses of the ORN to 103 compounds and discovered that certain human odorants elicit decreased responses after blood feeding, suggesting these human odorants are involved in Aedes aegypti host-seeking behaviors [21]. We hypothesize that chemical repellents exhibiting inhibitory effects (inhibitory chemical repellents) may interact with human odorants, resulting in the disruption of the mosqutoes’ olfactory recognition of human hosts and in diminished responses to them when mosquitoes are seeking feeding hosts. The proposed research objective is to determine the chemical repellents that affect a mosquito’s olfactory sense in order to prevent it from finding a human target or host. The proposed aims are to: 1) characterize the responses of Ae. aegypti ORs to inhibitory chemical repellents and to human odorants that may be involved in Ae. aegypti host-seeking and blood-feeding and 2) determine the competition effects of inhibitory chemical repellents and human odorants on Ae. aegypti ORs.

项目总结/摘要 拟议研究的长期目标是开发有效的替代化学驱避剂， 通过扰乱蚊子的人类气味来对抗蚊子的寄主寻找和吸血行为， 检测机制本提案中获得的信息将为化学品的开发提供信息。 避开已知的杀虫剂抗性机制以减少 蚊子传播的疾病和保护公众健康。 当寻找吸血食物时，蚊子依靠它们的嗅觉系统来检测化学气味 由他们发出的 人类宿主[8];这些人类气味剂有助于 不 蚊子传播 人类的疾病。使用化学驱避剂破坏蚊子的气味检测机制， 是目前杀虫剂的可行替代策略，如避蚊胺（第A.3节），用于脱敏 蚊子对人类的嗅觉需要更好地了解管理这些活动的机制， 化学驱避剂、寄主气味和蚊子嗅觉感受器反应之间的相互作用 能够开发新的驱虫剂替代品，使蚊子对人类不敏感，从而 干扰蚊子识别人类宿主。 在初步研究中，我们研究了48种驱避化学物质与嗅觉的相互作用， 受体神经元（ORN）的埃及伊蚊，并确定了几个萜烯/萜类化合物 对蚊子ORN表现出抑制作用[40]。我们进一步描述了ORN的反应 103种化合物，并发现某些人类气味在吸血后引起的反应减少， 这表明这些人类气味与埃及伊蚊寻找宿主的行为有关[21]。我们假设 显示抑制作用的化学驱避剂（抑制性化学驱避剂）可以与人类相互作用， 气味剂，导致清真寺对人类宿主的嗅觉识别中断， 当蚊子寻找食物宿主时，它们会做出反应。 拟议的研究目标是确定影响蚊子的化学驱避剂， 嗅觉，以防止它找到人类目标或宿主。拟议的目标是：1） 描述Ae的响应。抑制性化学驱避剂和人类气味剂， 可能与Ae有关。埃及伊蚊寄主寻找和吸血; 2）确定 抑制性化学驱避剂和人类气味剂对Ae.埃及珊瑚