Louisiana State University Agricultural Center, Department of Entomology, Baton Rouge, LA, United States of America.
Louisiana State University, School of Veterinary Medicine, Department of Pathobiological Sciences, Baton Rouge, LA, United States of America.
PLoS Negl Trop Dis. 2019 Feb 7;13(2):e0007153. doi: 10.1371/journal.pntd.0007153. eCollection 2019 Feb.
Tick feeding causes extreme morbidity and mortality to humans through transmission of pathogens and causes severe economic losses to the agricultural industry by reducing livestock yield. Salivary gland secretions are essential for tick feeding and thus, reducing or preventing saliva secretions into the vertebrate host is likely to reduce feeding and hinder pathogen life cycles. Unfortunately, the membrane physiology of tick salivary glands is underexplored and this gap in knowledge limits the development of novel therapeutics for inducing cessation of tick feeding.
We studied the influence of inward rectifier potassium (Kir) channel subtypes to the functional capacity of the isolated tick salivary gland through the use of a modified Ramsay assay. The secreted saliva was subsequently used for quantification of the elemental composition of the secreted saliva after the glands were exposed to K+ channel modulators as a measure of osmoregulatory capacity. Lastly, changes to blood feeding behavior and mortality were measured with the use of a membrane feeding system.
In this study, we characterized the fundamental role of Kir channel subtypes in tick salivary gland function and provide evidence that pharmacological inhibition of these ion channels reduces the secretory activity of the Amblyomma americanum salivary gland. The reduced secretory capacity of the salivary gland was directly correlated with a dramatic reduction of blood ingestion during feeding. Further, exposure to small-molecule modulators of Kir channel subtypes induced mortality to ticks that is likely resultant from an altered osmoregulatory capacity.
Our data contribute to understanding of tick salivary gland function and could guide future campaigns aiming to develop chemical or reverse vaccinology technologies to reduce the worldwide burden of tick feeding and tick-vectored pathogens.
蜱虫通过传播病原体导致人类罹患严重疾病甚至死亡，同时降低牲畜产量，给农业产业造成严重经济损失。唾液腺分泌对于蜱虫的取食至关重要，因此，减少或阻止唾液分泌到脊椎动物宿主中可能会降低取食并阻碍病原体的生命周期。不幸的是，蜱虫唾液腺的膜生理学研究还很不足，这一知识空白限制了开发用于诱导蜱虫停止取食的新型疗法。
我们通过使用改良的拉姆齐测定法，研究了内向整流钾 (Kir) 通道亚型对分离的蜱唾液腺功能能力的影响。随后，将腺体暴露于 K+通道调节剂后，使用分泌的唾液来定量分析分泌唾液的元素组成，作为对渗透调节能力的衡量。最后，使用膜饲养系统测量了血液取食行为和死亡率的变化。
在这项研究中，我们描述了 Kir 通道亚型在蜱唾液腺功能中的基本作用，并提供了证据表明，这些离子通道的药理学抑制可降低美洲钝缘蜱唾液腺的分泌活性。唾液腺分泌能力的降低与取食过程中血液摄入量的急剧减少直接相关。此外，暴露于 Kir 通道亚型的小分子调节剂会诱导蜱虫死亡，这可能是由于渗透调节能力改变所致。
我们的数据有助于了解蜱唾液腺的功能，并可能为未来旨在开发减少蜱虫取食和蜱传病原体的全球负担的化学或反向疫苗学技术的研究提供指导。
