Development of osmoregulation disruptors for tick control

项目摘要 蜱是专性体外寄生虫，以脊椎动物为食，并在吸血过程中传播病原体， 全球范围内的动物和人类健康问题。蜱传播各种各样的病原体，包括细菌（例如， 立克次氏体）、原生动物和病毒，并直接损害其宿主。一种最重要的蜱虫生理学允许蜱虫 在野外生存的关键是在整个生命周期中保持水平衡，包括非宿主时期。的 Metastriata蜱的饮水调节机制包括：1）通过肠道和唾液直接饮水 腺体，2）通过皮肤分泌失去大量的水，和3）随着代谢废物的排泄而失去水。 该提案的中心法则是利用蜱虫饮水行为作为将有毒物质传递给 破坏蜱虫的调节途径，这是一个脆弱的毒理学目标，在离开宿主蜱。充足的初步 数据为这一概念提供了证据。蜱虫死亡可以通过自愿饮用富含磷酸盐的等渗 溶液以及热诱导的耗尽性真皮分泌。这些建议的目的是发展蜱虫- 特异性呼吸调节干扰物（Aim 1），并研究蜱真皮分泌物失水的生理学 (Aim 2）。在本研究中，我们将研究无机磷代谢的生理和磷介导的 排泄系统中的电化学不平衡，其作为重要的排泄调节干扰物起作用。aim 2将 揭示真皮分泌的机制，包括降钙素介导的调节和离子转运机制， 真皮腺，这是一种独特的器官，在一秒钟内会损失大量（约300 nL）液体， 热/机械刺激。使用一个可调节的干扰物的策略非常适合在炎热和干燥的季节， 美国的中西部和西南部地区，有大量的转移条纹蜱、钝眼蜱、革蜱、扇头蜱， 和血蜱，并有病原体传播的报道。目前的建议是扩大知识 目标生理学，与开发环境相容的蜱虫控制的长期目标相联系 措施

Project Summary Ticks are obligatory ectoparasites that feed on vertebrates and transmit pathogens during blood feeding, causing health problems globally in animals and humans. Ticks transmit a wide variety of pathogens, including bacteria (e.g., rickettsia), protozoa, and viruses, and directly damage their hosts. A most significant tick physiology that allows ticks survive in the field is maintaining water balance throughout the lifetime including the off-host periods. The osmoregulatory mechanisms in Metastriata ticks include: 1) directly drinking water through the gut and the salivary glands, 2) losing large amounts of water through dermal secretion, and 3) losing water with excretion of metabolic wastes. The central dogma in this proposal is using the tick water drinking behavior as a route of delivering toxic agents to disrupt the osmoregulatory pathway, which is a vulnerable toxicological target in off-host ticks. Ample preliminary data provides the proof of the concept. Tick deaths could be induced by voluntary drinking of phosphate-rich iso-osmotic solutions and also by thermally induced exhaustive dermal secretion. The aims of the proposals are to develop the tick- specific osmoregulation disruptor (Aim 1) and to investigate the physiology of water loss through tick dermal secretion (Aim 2). In the Aim 1, we will study the physiology of the inorganic phosphate metabolism and phosphate-mediated electrochemical imbalance in the excretory system, which function as a significant osmoregulatory disruptor. Aim2 will uncover the mechanisms of dermal secretion including serotonin-mediated regulation and ion transport mechanisms in the dermal glands, which is a unique organ associated with a loss of large amount (~300 nL) of fluid within a second upon thermal/mechanical stimulation. The strategy using an osmoregulatory disruptor fits well in the hot and dry season in the Midwest and Southwest area of the U.S. where numerous Metastriata ticks, Amblyomma, Dermacentor, Rhipicephalus, and Haemaphysalis, and the pathogen transmission have been reported. The current proposal is to expand the knowledge of the target physiology, linking to the long-term goal in the development of environmentally compatible tick control measures.