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Lookup NU author(s): Chloe Ellison, Dr Curtis Cottam, Dr James ConnollyORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2026 Ellison et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Bacterial pathogens that infect host sites beyond their native ecological niche must be equipped to cope with unique challenges across distinct environments. This often manifests in the upregulation of virulence factors specifically in response to host cues, which enhance pathogen fitness. Extraintestinal pathogenic Escherichia coli (ExPEC) typically colonise the host-gut asymptomatically but can disseminate to infectious sites such as the bladder, kidneys and bloodstream. The molecular basis of urinary tract colonisation by ExPEC is well established, with adhesion via chaperone-usher fimbriae being a critical determinant. However, mechanisms that promote bloodstream infection are poorly understood. Here, we show that several ExPEC fimbriae are upregulated rapidly in response to human serum, mimicking exposure to the bloodstream environment. Yad fimbriae displayed the most significant induction in response to this host cue in two distinct ExPEC isolates, and we show that the gene cluster is prevalent across the E. coli phylogeny, suggesting a common virulence mechanism. Expression of Yad fimbriae was found to be repressed at the transcriptional level by the histone-like nucleoid structuring protein (H-NS). Furthermore, a prolonged elevation in Yad transcription was sustained throughout many generations of growth in serum, suggesting that cue(s) in the bloodstream counteract H-NS repression, triggering cell-surface expression of Yad fimbriae. Finally, Yad transcription was significantly upregulated within systemic tissue in a murine model of bacteremia and we show that deletion of the yad genes significantly attenuated ExPEC colonisation during infection. These data reveal Yad fimbriae as an important ExPEC virulence factor and support the concept of cellular adhesion as a crucial element of bacterial bloodstream pathogenesis.
Author(s): Ellison C, Cottam C, Lian ZJ, Onur T, Choudhury B, Ong YYT, Phan M-D, Schembri MA, Connolly JPR
Publication type: Article
Publication status: Published
Journal: PLOS Pathogens
Year: 2026
Volume: 22
Issue: 6
Online publication date: 01/06/2026
Acceptance date: 09/05/2026
Date deposited: 15/06/2026
ISSN (print): 1553-7366
ISSN (electronic): 1553-7374
Publisher: Public Library of Science
URL: https://doi.org/10.1371/journal.ppat.1014299
DOI: 10.1371/journal.ppat.1014299
Data Access Statement: All relevant data are within the manuscript and its Supporting Information files.
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