Development of osmoregulation disruptors for tick control

项目摘要 扁虱是一种必须的体外寄生虫，以脊椎动物为食，并在吸血过程中传播病原体，导致 全球动物和人类的健康问题。扁虱传播各种各样的病原体，包括细菌(例如， 立克次体)、原生动物和病毒，并直接损害它们的宿主。一种最重要的扁虱生理学，允许扁虱 在田间生存是在整个生命周期内保持水分平衡，包括在非寄主时期。这个 硬蜱的渗透调节机制包括：1)通过肠道和唾液直接饮用水 2)通过皮肤分泌物失去大量水分，3)随着代谢废物的排泄而失去水分。 这项提案的核心教条是利用扁虱饮水行为作为一种途径，将有毒物质输送到 破坏渗透调节途径，而渗透调节途径是非寄主扁虱的一个脆弱的毒理靶标。充分的初步资料 数据为这一概念提供了证据。如果自愿饮用富含磷酸盐的等渗液，可能会导致壁虱死亡 溶液和热诱导的穷尽的真皮分泌物。这些建议的目的是发展扁虱- 特异性渗透压调节干扰物(目标1)和研究硬蜱真皮分泌失水的生理学 (目标2)。在目标1中，我们将研究无机磷代谢和磷介导的生理学。 排泄系统中的电化学失衡，这是一个重要的渗透调节干扰物。AIM2将 揭示皮肤分泌的机制，包括5-羟色胺介导的调节和离子转运机制 真皮腺，这是一种独特的器官，与在一秒钟内失去大量液体(~300nL)有关 热/机械刺激。使用渗透调节干扰物的策略非常适合在炎热干燥的季节 美国中西部和西南部地区，在那里有大量的后生滴虫，Amblyomma，Dermacentor，Rhipicephalus， 和血腮腺炎，以及病原体的传播已有报道。目前的建议是扩大知识 目标生理学，与开发符合环境的壁虱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.