Human sweat taste and contact-guided behavior in Aedes aegypti

项目摘要 蚊子是每年向数亿人传播疾病的罪魁祸首。行为- 修改策略已成为监督和控制工作的主要工具。很多人都在关注 致力于阐明和操纵驱动宿主寻找的热感觉和嗅觉线索的检测 行为然而，在我们对蚊子-宿主接触化学感受的理解中存在着一个关键的空白 相互作用，尽管事实上，咬和吸血行为是驱动疾病的关键因素， 传输蚊子找到宿主后，会停在皮肤表面，检查皮肤表面，并对其进行探测 在开始吸血之前用她的管芯针众所周知，人体皮肤表面充满了 化学物质，包括汗液中的化学物质。了解人类的汗液是否可以通过 蚊子的味觉系统，如果是这样，这些线索是否激活了血液启动之前的行为 膳食，将提供一个有价值的切入点，为开发新的行为修改工具， 控制我们选择的型号是Ae。埃及伊蚊是登革热、基孔肯雅和寨卡病毒的载体， 对人类健康造成巨大的全球负担，现在也在一些地区建立了 美国的 我们建议探索这一假设，即存在于人类皮肤上的可溶性化合物是由 蚊子的味觉系统和激活近距离的行为之前，吸血。我们专注于人类 汗液成分，除了盐、酸和氨衍生物之外，还包括游离氨基酸。的 我们的假设背后的前提得到了我们的试点数据的支持，其中我们发现人工汗液混合物 以及某些氨基酸和盐可以激活雌性蚊子的味觉神经元。此外，本发明还 滤纸靶上呈现的混合物可以刺激交配雌性的相互作用和探测尝试。 我们建议的具体目标将通过两个目标来实现。在AIM 1中，我们将创建一个品味地图， 人类汗液成分和混合物在雌性埃及伊蚊中的响应性。我们将 确定这些刺激是否促进驻留或预喂养行为，例如使用标记和探测 独立的基于群体的和单个雌性行为测定。在AIM 2中，我们将评估细胞是否 并且通过敲除选定的味觉受体/共刺激物来改变对人类汗液促味剂的行为反应， CRISPR/Cas9介导的基因组编辑。拟议研究的结果将提供 重要的分子和神经生理学的见解蚊子的味道引导的行为引起的 人体汗液中发现的化合物

PROJECT SUMMARY Mosquitoes are responsible for transmitting disease to hundreds of millions of people each year. Behavior- modification strategies have been major tools in surveillance and control efforts. A lot of attention has been devoted to elucidating and manipulating detection of thermosensory and olfactory cues that drive host-seeking behavior. However, a critical gap exists in our understanding of contact chemosensation in mosquito-host interactions, despite the fact that biting and blood feeding behaviors are crucial factors in driving disease transmission. After a mosquito has found a host, she lands on and examines the skin surface, and probes it with her stylets before initiating a blood meal. It is well known that the human skin surface is replete with chemicals, including those found in sweat. An understanding of whether human sweat cues can be sensed by the mosquito taste system, and if so, whether these cues activate behaviors that precede initiation of blood meals, would provide a valuable entry point for developing new behavior-modifying tools for surveillance and control. Our model of choice is Ae. aegypti, a vector of Dengue, Chikungunya, and Zika viruses, which is responsible for an enormous worldwide burden on human health, and is now also established in some regions of the United States. We propose to explore the hypothesis that soluble compounds present on human skin are sensed by the mosquito taste system and activate close-range behaviors that precede blood feeding. We focus on human sweat components, which include free amino acids in addition to salts, acids and ammonia derivatives. The premise behind our hypothesis is supported by our pilot data, in which we find that an artificial sweat mixture as well as certain individual amino acids and salt can activate taste neurons in female mosquitoes. Further, mixtures presented on a filter paper target can stimulate interaction and probing attempts in mated females. The specific goals of our proposal will be accomplished via two aims. In AIM 1, we will create a map of taste responsivity of human sweat components and mixtures in the female Aedes aegypti mosquito. We will determine if these stimuli promote residency or pre-feeding behaviors such as labellating and probing using independent population-based and single-female behavior assays. In AIM 2, we will evaluate whether cellular and behavioral responses to human sweat tastants are altered by knocking out selected taste receptors/co- receptors using CRISPR/Cas9-mediated genome editing. The results of the proposed studies will provide important molecular and neurophysiological insights into mosquito taste-guided behaviors elicited by compounds found in human sweat.