Selective cysteine protease inhibition contributes to blood-feeding success of the tick Ixodes scapularis
Selective cysteine protease inhibition contributes to blood-feeding success of the tick Ixodes scapularis
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DOI：
10.1074/jbc.m703143200
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发表时间：
2007-10-05
影响因子：
4.8
通讯作者：
Ribeiro, Jose M. C.
中科院分区：
文献类型：
--
作者：
Kotsyfakis, Michalis;Karim, Shahid;Ribeiro, Jose M. C.
肩突硬蜱是美国东部和中部莱姆病的主要传播媒介。蜱的唾液分泌已被证明对血餐完成和病原体传播都很重要。在这里，我们报告了其基因组中的半胱氨酸蛋白酶抑制剂基因的重复事件，导致在血液喂养过程中对保守和相对有限数量的脊椎动物木瓜蛋白酶样半胱氨酸蛋白酶的唾液抑制活性的转录调节增强。我们进一步表明，这两个基因的多肽产物不同的结合亲和力的一些酶的目标，它们显示不同的抗原性。此外，我们采用RNA干扰的反向遗传方法发现了蜱虫喂养成功的关键调解。考虑到靶向酶在脊椎动物免疫中的作用，我们还表明宿主免疫调节与沉默蜱的有害表型有关。肩胛肌胱抑素是抗蜱疫苗开发的有吸引力的靶点。
Ixodes scapularis is the main vector of Lyme disease in the eastern and central United States. Tick salivary secretion has been shown as important for both blood-meal completion and pathogen transmission. Here we report a duplication event of cystatin genes in its genome that results in a transcription-regulated boost of saliva inhibitory activity against a conserved and relatively limited number of vertebrate papain-like cysteine proteases during blood feeding. We further show that the polypeptide products of the two genes differ in their binding affinity for some enzyme targets, and they display different antigenicity. Moreover, our reverse genetic approach employing RNA interference uncovered a crucial mediation in tick-feeding success. Given the role of the targeted enzymes in vertebrate immunity, we also show that host immunomodulation is implicated in the deleterious phenotype of silenced ticks making I. scapularis cystatins attractive targets for development of antitick vaccines.