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Simple Summary: Ticks are responsible for transmitting several disease-causing agents to humans and animals, including those causing Lyme disease and Rocky Mountain spotted fever. Human protection from tick bites relies on personal protection tactics for preventing or minimizing tick feeding. One common method is the use of chemicals for repelling or killing ticks. This study sought to assess the repellent capability of the tick-killing compound, nootkatone, which is found in natural sources like grapefruit oil, against adult ticks in a laboratory setting. Nootkatone can be found in two main structural arrangements in nature, resulting in the ability to distinguish between a (+) isomer and a (−) isomer. The (+) isomer has a lower odor threshold (and is therefore more potent in its fragrance) and was chosen for use in this study. Adult females of three tick species, the American dog tick (Dermacentor variabilis), the blacklegged tick (Ixodes scapularis), and the lone star tick (Amblyomma americanum), were repelled by nootkatone at different concentrations. Blacklegged ticks were most susceptible to this compound, not only being repelled at very low nootkatone concentrations, but also experiencing significant mortality when checked 24 h after exposure. American dog ticks and lone star ticks required much higher concentrations to repel and were not killed by the brief exposures. These experimental results indicate that nootkatone may be used in a dual action killing/repelling role against adult ticks, with particularly strong effects against blacklegged ticks. Ticks are vectors of many human and animal zoonotic disease-causing agents causing significant global health and economic strain. Repellents and acaricides are integral to the human capacity for personal protection from tick bites. Nootkatone, a naturally occurring sesquiterpene found in the Alaskan cedar tree, grapefruit, and other sources, has been documented to be a potent acaricide. Research has also noted repellent effects against some tick species. In this study, our aim was to investigate the effect of synthetic, high-purity (+)-nootkatone on adult Ixodes scapularis, Dermacentor variabilis, and Amblyomma americanum ticks in an in vitro, vertical filter paper bioassay. (+)-nootkatone showed compelling tick repellency, but median effective concentrations (EC50) significantly differed among species. Ixodes scapularis were repelled at very low concentrations (EC50 = 0.87 ± 0.05 µg/cm2). Higher concentrations were required to repel D. variabilis (EC50 = 252 ± 12 µg/cm2) and A. americanum (EC50 = 2313 ± 179 µg/cm2). Significant post-exposure mortality, assessed 24 h after repellency trials, was also observed in I. scapularis but was absent entirely in D. variabilis and A. americanum. These tests demonstrate that nootkatone has a promising dual-action personal protection capacity against adult I. scapularis ticks, warranting further investigation in more natural environments and in the presence of host cues. [ABSTRACT FROM AUTHOR] |