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

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.