Development of osmoregulation disruptors for tick control

开发用于蜱控制的渗透调节干扰剂

• 批准号: 10432104
• 负责人: Yoonseong Park
• 金额: $ 22.8万
• 依托单位: KANSAS STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-06-16 至 2023-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10432104
• 关键词: Adult; Amblyomma; Ambylomma americanum; Anatomy; Animals; Area; Bacteria; Bioinformatics; Blood; Cessation of life; Data; Dermacentor; Dermal; Development; Environmental Risk Factor; Equilibrium; Excretory function; Formulation; Foundations; Funding; Genes; Genome; Gland; Goals; Health; Hemolymph; Hormonal; Human; Immunohistochemistry; In Situ Hybridization; Inorganic Phosphate Transporter; Investigation; Ion Transport; Ixodes; Knowledge; Lead; Link; Liquid substance; Measures; Mechanical Stimulation; Mechanics; Mediating; Metabolic; Metabolism; Midwestern United States; Molecular; Na(+)-K(+)-Exchanging ATPase; Nymph; Organ; Osmoregulation; Ouabain; Pathway interactions; Pharmacology; Pharmacology Study; Physiology; Poison; Precipitation; Process; Protozoa; Publications; Regulation; Reporting; Rhipicephalus; Rickettsia; Route; Salivary Glands; Seasons; Serotonin; Signal Pathway; Sodium; System; Testing; Tick Control; Ticks; Tissues; Toxic Actions; Toxic effect; Toxicology; Transcript; Vertebrates; Virus; Water; combinatorial; drinking; drinking behavior; drinking water; exhaustion; feeding; inorganic phosphate; ionic balance; mechanical stimulus; novel; pathogen; saliva secretion; serotonin receptor; synergism; tick transmission; tool; transmission process; wasting; water drinking behavior

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.

项目概要 蜱虫是强制性的体外寄生虫，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。蜱传播多种病原体，包括细菌（例如， 立克次体）、原生动物和病毒，并直接损害其宿主。允许蜱虫生长的最重要的蜱虫生理学 在野外生存需要在整个生命周期（包括脱离寄主期间）保持水平衡。这 后纹蜱的渗透压调节机制包括：1）通过肠道和唾液直接饮水 腺体，2）通过真皮分泌流失大量水分，3）通过代谢废物的排泄流失水分。 该提案的中心法则是利用蜱虫的饮水行为作为向人体输送有毒物质的途径。 破坏渗透调节途径，这是脱离宿主蜱的一个脆弱的毒理学目标。充足的初步 数据提供了概念的证明。自愿饮用富含磷酸盐的等渗水可能会导致蜱死亡 溶液以及热诱导的彻底真皮分泌。这些提案的目的是发展蜱虫 特定渗透调节干扰物（目标 1）并研究蜱真皮分泌导致失水的生理学 （目标 2）。在目标 1 中，我们将研究无机磷酸盐代谢和磷酸盐介导的生理学 排泄系统中的电化学失衡，是一种重要的渗透调节干扰物。目标2将 揭示真皮分泌机制，包括血清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，与在一秒钟内流失大量（约 300 nL）液体有关 热/机械刺激。使用渗透调节干扰剂的策略非常适合炎热和干燥的季节 美国中西部和西南部地区有大量的后纹蜱、Amblyomma、Dermacentor、Rhipicephalus、 和血蜱，以及病原体传播已有报道。目前的建议是扩大知识面 目标生理学的目标，与开发环境相容的蜱虫控制的长期目标相联系 措施。

项目成果

Characterization of Iflavirus in the Red Flour Beetle, Tribolium castaneum (Coleoptera; Tenebrionidae).

• DOI: 10.3390/insects14030220
• 发表时间: 2023-02-23
• 期刊: Insects
• 影响因子: 3
• 作者: Fatehi S;Aikins M;Philips TW;Brown S;Zhu KY;Scully ED;Park Y
• 通讯作者: Park Y

Bee-safe peptidomimetic acaricides achieved by comparative genomics.

• DOI: 10.1038/s41598-022-20110-0
• 发表时间: 2022-10-14
• 期刊: SCIENTIFIC REPORTS
• 影响因子: 4.6
• 作者: Jindal, Vikas;Li, Daqi;Rault, Leslie C.;Fatehi, Soheila;Singh, Rupinder;Mating, Moritz;Zou, Ye;Ng, Ho-Leung;Kaczmarek, Krzysztof;Zabrocki, Janusz;Gui, Shunhua;Smagghe, Guy;Anderson, Troy D.;Nachman, Ronald J.;Park, Yoonseong
• 通讯作者: Park, Yoonseong

Water absorption through salivary gland type I acini in the blacklegged tick, Ixodes scapularis.

• DOI: 10.7717/peerj.3984
• 发表时间: 2017
• 期刊: PeerJ
• 影响因子: 2.7
• 作者: Kim D;Maldonado-Ruiz P;Zurek L;Park Y
• 通讯作者: Park Y

The bacterial community of the lone star tick (Amblyomma americanum).

• DOI: 10.1186/s13071-020-04550-z
• 发表时间: 2021-01-14
• 期刊: Parasites & vectors
• 影响因子: 3.2
• 作者: Maldonado-Ruiz LP;Neupane S;Park Y;Zurek L
• 通讯作者: Zurek L

Diversity of the Bacterial and Viral Communities in the Tropical Horse Tick, Dermacentor nitens, in Colombia.

• DOI: 10.3390/pathogens12070942
• 发表时间: 2023-07-16
• 期刊: Pathogens (Basel, Switzerland)