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Although <jats:italic>Escherichia coli<\/jats:italic> (<jats:italic>E. coli<\/jats:italic>) 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 <jats:italic>E. coli<\/jats:italic> 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 <jats:italic>E. coli<\/jats:italic> infection. Our findings support an Egr-1-dependent mechanism of BBB disruption by meningitic <jats:italic>E. coli<\/jats:italic>, highlighting a promising therapeutic target for bacterial meningitis.<\/jats:p>","DOI":"10.1186\/s12964-024-01488-y","type":"journal-article","created":{"date-parts":[[2024,1,17]],"date-time":"2024-01-17T19:02:07Z","timestamp":1705518127000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Egr-1 is a key regulator of the blood-brain barrier damage induced by meningitic Escherichia coli"],"prefix":"10.1186","volume":"22","author":[{"given":"Ruicheng","family":"Yang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyi","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hulin","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaqi","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Tan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huanchun","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangru","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,1,17]]},"reference":[{"key":"1488_CR1","doi-asserted-by":"publisher","first-page":"103274","DOI":"10.1016\/j.ebiom.2021.103274","volume":"65","author":"K Diallo","year":"2021","unstructured":"Diallo K, Feteh VF, Ibe L, Antonio M, Caugant DA, du Plessis M, Deghmane AE, Feavers IM, Fernandez K, Fox LM, et al. 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