Ansari Moiz Ashraf, Nguyen Thu-Thuy, Kocurek Klaudia Izabela, Kim William Tae Heung, Kim Tae Kwon, Mulenga Albert
Department of Veterinary Pathobiology, School of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX 77843, USA.
Department of Chemistry, Texas A&M University, College Station, TX 77843, USA.
Pathogens. 2024 Jul 3;13(7):560. doi: 10.3390/pathogens13070560.
is a blood-feeding obligate ectoparasite responsible for transmitting the Lyme disease (LD) agent, . During the feeding process, injects into the host along with its saliva, facilitating the transmission and colonization of the LD agent. Tick calreticulin (CRT) is one of the earliest tick saliva proteins identified and is currently utilized as a biomarker for tick bites. Our recent findings revealed elevated levels of CRT in the saliva proteome of -infected nymphs compared to uninfected ticks. Differential precipitation of proteins (DiffPOP) and LC-MS/MS analyses were used to identify the interactions between () CRT and human plasma proteins and further explore its potential role in shielding from complement killing. We observed that although yeast-expressed recombinant (r) CRT binds to the C1 complex (C1q, C1r, and C1s), the activator of complement via the classical cascade, it did not inhibit the deposition of the membrane attack complex (MAC) via the classical pathway. Intriguingly, rCRT binds intermediate complement proteins (C3, C5, and C9) and reduces MAC deposition through the lectin pathway. Despite the inhibition of MAC deposition in the lectin pathway, rCRT did not protect a serum-sensitive strain (B314/pBBE22) from complement-induced killing. As establishes a local dermal infection before disseminating to secondary organs, it is noteworthy that rCRT promotes the replication of in culture. We hypothesize that rCRT may contribute to the transmission and/or host colonization of by acting as a decoy activator of complement and by fostering replication at the transmission site.
是一种吸血性专性体外寄生虫，负责传播莱姆病（LD）病原体。在进食过程中，会将病原体连同其唾液一起注入宿主体内，促进LD病原体的传播和定植。蜱钙网蛋白（CRT）是最早被鉴定出的蜱唾液蛋白之一，目前被用作蜱叮咬的生物标志物。我们最近的研究结果显示，与未感染的蜱相比，感染病原体的若蜱唾液蛋白质组中CRT水平升高。采用蛋白质差异沉淀法（DiffPOP）和液相色谱-串联质谱分析来鉴定蜱（）CRT与人类血浆蛋白之间的相互作用，并进一步探讨其在保护病原体免受补体杀伤方面的潜在作用。我们观察到，尽管酵母表达的重组（r）CRT通过经典途径与补体激活剂C1复合物（C1q、C1r和C1s）结合，但它并未抑制膜攻击复合物（MAC）通过经典途径的沉积。有趣的是，rCRT与补体中间蛋白（C3、C5和C9）结合，并通过凝集素途径减少MAC沉积。尽管rCRT抑制了凝集素途径中MAC的沉积，但它并未保护血清敏感的菌株（B314/pBBE22）免受补体诱导的杀伤。由于病原体在扩散到次要器官之前先建立局部皮肤感染，值得注意的是，rCRT促进了病原体在培养中的复制。我们假设，rCRT可能通过充当补体的诱饵激活剂以及促进病原体在传播部位的复制，从而有助于病原体的传播和/或宿主定植。
