Development of osmoregulation disruptors for tick control

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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.