Mihaljica Darko, Repac Jelena, Božić Bojan, Marković Dragana, Radulović Željko, Mulenga Albert, Sukara Ratko, Veinović Gorana, Nedeljković Biljana Božić, Tomanović Snežana
Group for Medical Entomology, Centre of Excellence for Food- and Vector-Borne Zoonoses, Institute for Medical Research, National Institute of Republic of Serbia, University of Belgrade, Belgrade, Serbia.
Institute for Physiology and Biochemistry "Ivan Djaja", University of Belgrade, Belgrade, Serbia.
Exp Appl Acarol. 2025 Jan 28;94(2):31. doi: 10.1007/s10493-025-01001-1.
Tick salivary proteins are crucial for efficient and successful tick feeding. Most of them are still uncharacterized, especially those involved in the formation of tick cement. Tick salivary protein PA107 is a putative cement protein, which is transcribed in salivary glands during the initial phase of tick feeding. It is a tick-unique protein, with homologs described in several tick genera. In this study, a detailed in silico analysis of its primary and tertiary structure was performed, along with the immunogenicity assessment for the PA107 protein from Ixodes ricinus species. The screening of the primary structure placed it to the glycine-rich protein family, revealing in parallel an overlapping 15mer at the C-terminus and borderline homology to non-tick proteins with antimicrobial activity. The analysis of tertiary structure revealed a high degree of intrinsic disorder for monomeric PA107, in contrast to highly ordered structures for different oligomeric states that might correlate with the putative role in the tick cement formation process. Regarding in silico PA107 immunogenicity inference, obtained results were inconclusive, which aligns with the in vitro findings showing definitely the lack of humoral response induction in experimentally infested rats and persons bitten by the I. ricinus ticks. The results represent new pieces of a huge puzzle depicting a complex tick-host relationship, but also identify PA107 as a possible compound of novel formulations to be used in biomedicine as bioadhesives, and as a target for new anti-tick strategies, by interfering with the cement cone formation and stability, i.e. tick attachment and feeding.
蜱唾液蛋白对于蜱高效且成功地进食至关重要。其中大多数蛋白仍未得到表征,尤其是那些参与蜱黏合剂形成的蛋白。蜱唾液蛋白PA107是一种假定的黏合剂蛋白,在蜱进食初期于唾液腺中转录。它是一种蜱特有的蛋白,在几个蜱属中都有同源物被描述。在本研究中,对其一级和三级结构进行了详细的计算机模拟分析,同时对蓖麻硬蜱的PA107蛋白进行了免疫原性评估。一级结构筛选将其归入富含甘氨酸的蛋白家族,同时在C端发现了一个重叠的15聚体,并且与具有抗菌活性的非蜱蛋白存在边缘同源性。三级结构分析显示,单体PA107具有高度的内在无序性,与之形成对比的是,不同寡聚状态的结构高度有序,这可能与在蜱黏合剂形成过程中的假定作用相关。关于计算机模拟的PA107免疫原性推断,所得结果尚无定论,这与体外研究结果一致,体外研究明确表明,在实验性感染的大鼠和被蓖麻硬蜱叮咬的人中未诱导出体液反应。这些结果代表了描绘复杂蜱 - 宿主关系的巨大拼图中的新碎片,但同时也将PA107确定为生物医学中用作生物黏合剂的新型制剂的可能成分,以及通过干扰黏合锥的形成和稳定性(即蜱的附着和进食)来制定新的抗蜱策略的靶点。