Identification of a mechanical signaling pathway activating type 1 fimbriae via a ZraSR two-component system in neonatal meningitis-associated <i>Escherichia coli</i>.

Overview

1. National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, TEDA Institute of Biological Sciences and Biotechnology, Nankai University, Tianjin, China
2. The Key Laboratory of Molecular Microbiology and Technology, Ministry of Education, Nankai University, Tianjin, China
3. Chinese Academy of Medical Sciences, State Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, Tianjin, China
4. Department of Critical Care Medicine, Children’s Hospital of Tianjin University/Tianjin Children’s Hospital, Tianjin, China
5. Nankai International Advanced Research Institute, Nankai University, Shenzhen, China

Abstract

Escherichia coli K1 (E. coli K1) meningitis develops after the bacteria cross the blood−brain barrier (BBB); however, the molecular mechanisms underlying this process remain incompletely understood. Adhesion to human brain microvascular endothelial cells (HBMECs), which constitute the BBB, is considered important in E. coli K1 bacterial penetration into the central nervous system. Here, we report a complete signal regulatory pathway in which the ZraSR two-component system (TCS) senses mechanical cues-specifically, physical forces and envelope perturbations generated by the initial attachment of E. coli K1 to host cells-and directly binds to fimS, the invertible promoter element of the fim operon (fimAICDFGH). This interaction promotes fimS inversion to the phase-ON orientation, thereby activating the expression of type 1 fimbriae, specifically the FimH adhesin. This activation enhances E. coli K1 invasion into HBMECs. Disruption of this signaling pathway severely attenuates the progression of meningitis and reduces the production of proinflammatory factors triggered by E. coli K1 infection in vivo. These findings suggest that components of this pathway may serve as potential targets for novel therapeutic strategies against E. coli K1 infection.

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

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Data

Datasets cited

• figshare:31054993, at figshare; found in “Data availability statement”
• figshare:33614273, at figshare; found in DataCite

Data availability statement

RNA-seq data have been deposited in the NCBI SRA database under accession code PRJNA1392831. All raw data and supplementary materials supporting the findings of this study are openly available in figshare at https://doi.org/10.6084/m9.figshare.31054993 [57].

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

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Version 3, 28 September 2026

• Funding: added Johns Hopkins University; National Natural Science Foundation of China: JCYJ20230807151559009, 82402643, 82572591, W2512084, JCYJ20220530164604010, 82372267; Basic and Applied Basic Research Foundation of Guangdong Province: 2024A1515010588

Version 1, 27 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 12 authors, 6 keywords, 14 MeSH terms, 57 references.

Cite

This paper

Li, X., Wang, J., Li, Z., Guo, X., Wang, Y., Chen, X., Zheng, Y., Zhang, Q., Liu, R., Sun, X., Liu, B., & Sun, H. (2026). Identification of a mechanical signaling pathway activating type 1 fimbriae via a ZraSR two-component system in neonatal meningitis-associated <i>Escherichia coli</i>. Virulence, 17(1), 2721762. https://doi.org/10.1080/21505594.2026.2721762

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