红斑丹毒丝菌胆碱结合蛋白Cbp B的致病机制研究

Swine erysipelas is an important infectious disease caused by Erysipelothrix rhusiopathiae and seriously threatens the swine industry in the world. Recent years, there is an increased trend in the incidence of infection. The pathogenic mechanisms of swine erysipelas are poorly understood. Previously, we found a protein in Erysipelothrix rhusiopathiae, Cbp B, which can adhere to vascular endothelial cells of swine in vitro. In addition, Cbp B protein acts as a vital ligand by binding to an important component of extracelluar matrix, fibronection. However, it’s role in the pathogenesis of Erysipelothrix rhusiopathiae is still unknown. In the present study, we will study the effect of Cbp B protein on the virulence, adhesion, invasion, and antiphagocytosis of Erysipelothrix rhusiopathiae. Besides, we intend to reveal the role of Cbp B protein in activation and evasion in complement-mediated killer process as well as the role of Cbp B protein in helping Erysipelothrix rhusiopathiae to evade immunity. We will define the mechanism of Erysipelothrix rhusiopathiae in host infection and pathogenesis through studying the role of Cbp B protein in immune escape caused by Erysipelothrix rhusiopathiae. Our study will provide scientific evidence for developing vaccine and diagnostic method of Erysipelothrix rhusiopathiae.

猪丹毒是世界范围内严重危害养猪业的一种重要传染病，近几年来其感染发生率又呈上升趋势。该病的基础性研究较为匮乏，本课题组前期发现红斑丹毒丝菌Cbp B蛋白体外能黏附猪的血管内皮细胞，并能作为红斑丹毒丝菌的配体招募宿主的血纤维蛋白溶酶原和纤连蛋白，但该蛋白在感染和致病中扮演的角色还不清楚。为此，本项目拟以红斑丹毒丝菌Cbp B为研究对象，探讨Cbp B对红斑丹毒丝菌毒力的影响和在红斑丹毒丝菌黏附、侵入宿主细胞和抗吞噬中扮演的角色，及其在红斑丹毒丝菌激活和逃避补体介导的杀伤过程中的作用。通过研究Cbp B在红斑丹毒丝菌免疫逃避过程中发挥的作用，从而揭示Cbp B在红斑丹毒丝菌对宿主感染和致病过程中的机制。为研究和开发新型红斑丹毒丝菌疫苗和诊断方法提供科学依据。

猪丹毒近年在我国频发爆发，属于“老病新发”。虽然对该病的重视程度已逐渐增加，但由于其致病机制仍然处于未知阶段，导致不能很好的治疗和控制该病。目前，针对红斑丹毒丝菌如何侵袭宿主并逃避宿主天然免疫的清除和杀灭机制鲜为人知。本研究利用第三代测序技术，对分离的SE38强毒株和我国经典的疫苗毒株G4T10菌株进行全基因组测序，通过比较这两个菌株之间的基因组差异，选出差异基因CbpB。研究发现CbpB不仅可以特异性地结合到猪血管内皮细胞上去，而且可以竞争性抑制红斑丹毒丝菌粘附宿主细胞，也就是说CbpB在红斑丹毒丝菌粘附猪血管内皮细胞过程中可以直接发挥粘附素的作用。进一步的研究表明CbpB可以和血浆纤维蛋白溶解酶原发生特异性结合，这就表明CbpB在红斑丹毒丝菌招募血浆纤维蛋白溶解酶原过程中可能发挥受体作用，红斑丹毒丝菌可能利用这个宿主分子在定植、入侵、炎症、免疫调节中发挥作用。本项目研究成果为阐明红斑丹毒丝菌的致病机理奠定基础，为猪丹毒的防控提供新的候选诊断标识和药物靶点。本项目研究成果为阐明红斑丹毒丝菌的致病机理奠定基础，为猪丹毒的防控提供新的候选诊断标识和药物靶点。已发表会议论文2篇；获国家授权发明专利1项；湖北省地方标准1项；培养博士后1名，在读博士研究生1名。