Bacterial meningitis remains a leading cause of infection-related mortality worldwide. Although Escherichia coli ( E. coli ) is the most common etiology of neonatal meningitis, the underlying mechanisms governing bacterial blood-brain barrier (BBB) disruption during infection remain elusive. We observed that infection of human brain microvascular endothelial cells with meningitic E. coli triggers the activation of early growth response 1 (Egr-1), a host transcriptional activator. Through integrated chromatin immunoprecipitation sequencing and transcriptome analysis, we identified Egr-1 as a crucial regulator for maintaining BBB integrity. Mechanistically, Egr-1 induced cytoskeletal changes and downregulated tight junction protein expression by directly targeting VEGFA, PDGFB, and ANGPTL4, resulting in increased BBB permeability. Meanwhile, Egr-1 also served as a master regulator in the initiation of neuroinflammatory response during meningitic E. coli infection. Our findings support an Egr-1-dependent mechanism of BBB disruption by meningitic E. coli , highlighting a promising therapeutic target for bacterial meningitis. Supplementary Information The online version contains supplementary material available at 10.1186/s12964-024-01488-y.
【저자키워드】 Neuroinflammation, blood-brain barrier, permeability, early growth response 1, Meningitic E. Coli,