Integrated transcriptomic and proteomic analysis reveals inflammatory activation and blood-brain barrier disruption during meningitis-associated extraintestinal pathogenic <i>Escherichia coli</i> infection.

Overview

1. Joint International Research Laboratory of Animal Health and Animal Food Safety, College of Veterinary Medicine, Southwest University, Chongqing, China
2. National Center of Technology Innovation for Pigs, Chongqing, China
3. Division of Infectious Diseases and Geographic Medicine, Department of Medicine, Stanford University, Stanford, CA, USA

Abstract

Meningitis-associated extraintestinal pathogenic Escherichia coli (ExPEC) is a major cause of bacterial meningitis, yet the molecular mechanisms underlying blood-brain barrier (BBB) disruption during infection remain unclear. We employed integrated transcriptomic and proteomic analysis to investigate host responses of human cerebral microvascular endothelial cell line hCMEC/D3 to ExPEC strain RS218 infection. Multi-omics integration revealed coordinated immune activation, with upregulation of innate immune signaling pathways such as Toll-like receptor, NOD-like receptor, TNF, and IL-1 signaling, as well as antigen presentation pathways. In addition, we identified direct molecular evidence for BBB compromise, including concordant downregulation of tight junction protein ZO-1 at both transcriptomic and proteomic levels, validated by immunofluorescence showing reduced ZO-1 expression in infected cells. Several processes that may contribute to BBB breakdown were identified, such as glycosaminoglycan degradation, cytoskeletal reorganization, and suppression of TGF-β/SMAD signaling. Moreover, extensive metabolic dysregulation was evident, including downregulation of neural metabolic support functions and compromised protein homeostasis. Abundant discordance between transcriptomic and proteomic levels revealed complex post-transcriptional control mechanisms. In vitro experiments demonstrated RS218-induced cell death in brain endothelial cells, microglial cells, and peritoneal macrophages. Animal experiments confirmed systemic metabolic disruption, immune cell alteration, functional BBB disruption, and profound brain cytokine elevation. This integrated analysis advances our understanding of bacterial meningitis pathogenesis and identifies potential therapeutic targets.

Reproduced under the paper's license (CC BY), from the paper cited above.

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Data

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• figshare:30338854, at figshare; found in “Data availability statement”

Data availability statement

The RNA-seq data for this study have been deposited in the European Nucleotide Archive (ENA) at EMBL-EBI under accession number PRJEB94539. The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE [32] partner repository with the dataset identifier PXD066627. Raw and supplementary data for this study are available at Figshare (DOI: 10.6084/m9.figshare.30338854 (https://doi.org/10.6084/m9.figshare.30338854)).

Reproduced under the paper's license (CC BY), from the paper cited above.

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Version 1, 28 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 9 authors, 5 keywords, 16 MeSH terms, 5 funders, 47 references.

Cite

This paper

Li, Z., Chen, M., Du, Y., Jia, K., Lu, Y., Yu, X., Cao, X., Peng, L., & Fang, R. (2026). Integrated transcriptomic and proteomic analysis reveals inflammatory activation and blood-brain barrier disruption during meningitis-associated extraintestinal pathogenic <i>Escherichia coli</i> infection. Virulence, 17(1), 2670939. https://doi.org/10.1080/21505594.2026.2670939

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