烯醇化酶介导细菌突破血脑屏障的分子机制

Molecular mechanisms of enolase-mediated bacterial penetration of the blood-brain barrier

摘要:

细菌性脑膜炎具有高致死率且易引发严重后遗症，阐明细菌穿越血脑屏障(blood-brain barrier, BBB)的分子机制，对人和动物脑膜炎的防控具有重要理论与实践意义。烯醇化酶(enolase，ENO)作为多种病原菌的关键毒力因子，在突破 BBB过程中发挥着核心作用。本文聚焦ENO介导BBB破坏的分子机制，从病原-宿主互作的角度，系统综述了ENO通过识别脑微血管内皮细胞(brain microvascular endothelial cells, BMECs)表面受体、诱导宿主细胞相分离与膜复合体组装、劫持纤溶系统、调控细胞骨架及紧密连接以及干预免疫炎症反应等多条路径协同破坏BBB完整性的研究进展；展望了基于ENO的靶向干预策略(如小分子抑制剂、纳米抗体、疫苗)在细菌性脑膜炎防控中的应用前景，为新型抗感染策略的制定提供了科学依据。

Abstract:

Bacterial meningitis is associated with a high mortality and frequently leads to severe sequelae. Elucidating the molecular mechanisms underlying bacterial traversal of the blood-brain barrier (BBB) holds significant theoretical and practical value for the prevention and control of meningitis in both humans and animals. As a key virulence factor conserved in various pathogenic bacteria, enolase (ENO) plays a pivotal role in the process of BBB penetration. This review focuses on the molecular mechanisms of ENO-mediated BBB disruption. From the perspective of pathogen-host interactions, it systematically summarizes the recent research progress on the multiple pathways through which ENO impairs BBB integrity, including recognition and binding to receptors on brain microvascular endothelial cells (BMECs), induction of host cell phase separation and membrane complex assembly, hijacking of the fibrinolytic system, regulation of the cytoskeleton and tight junction integrity, and modulation of immune-inflammatory responses. Furthermore, this review discusses the application prospects of ENO-based targeted intervention strategies, such as small-molecule inhibitors, nanobodies, and vaccines, in the prevention and control of bacterial meningitis, with the aim of providing a scientific foundation for the development of novel anti-infection strategies against this devastating disease.