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Lookup NU author(s): Dr James ConnollyORCiD, Andrew Roe
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
Copyright: © 2024 Wale 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. The ability of the attaching and effacing pathogens enterohaemorrhagic Escherichia coli (EHEC) and Citrobacter rodentium to overcome colonisation resistance is reliant on a type 3 secretion system used to intimately attach to the colonic epithelium. This crucial virulence factor is encoded on a pathogenicity island known as the Locus of Enterocyte Effacement (LEE) but its expression is regulated by several core-genome encoded transcription factors. Here, we unveil that the core transcription factor PdhR, traditionally known as a regulator of central metabolism in response to cellular pyruvate levels, is a key activator of the LEE. Through genetic and molecular analyses, we demonstrate that PdhR directly binds to a specific motif within the LEE master regulatory region, thus activating type 3 secretion directly and enhancing host cell adhesion. Deletion of pdhR in EHEC significantly impacted the transcription of hundreds of genes, with pathogenesis and protein secretion emerging as the most affected functional categories. Furthermore, in vivo studies using C. rodentium, a murine model for EHEC infection, revealed that PdhR is essential for effective host colonization and maximal LEE expression within the host. Our findings provide new insights into the complex regulatory networks governing bacterial pathogenesis. This research highlights the intricate relationship between virulence and metabolic processes in attaching and effacing pathogens, demonstrating how core transcriptional regulators can be co-opted to control virulence factor expression in tandem with the cell’s essential metabolic circuitry.
Author(s): Wale KR, Boyle NO, McHugh R, Serrano E, Mark D, Douce GR, Connolly JPR, Roe AJ
Publication type: Article
Publication status: Published
Journal: PLoS Pathogens
Year: 2024
Volume: 20
Issue: 10
Online publication date: 15/10/2024
Acceptance date: 01/10/2024
Date deposited: 04/11/2024
ISSN (print): 1553-7366
ISSN (electronic): 1553-7374
Publisher: Public Library of Science
URL: https://doi.org/10.1371/journal.ppat.1012451
DOI: 10.1371/journal.ppat.1012451
Data Access Statement: The RNA-seq data is available from the European Nucleotide Archive under the accession number PRJEB74273. Publicly available genome sequences were obtained from the NCBI Sequence Read Archive. Each of these genomes can be readily accessed from the accession numbers provided in S5 Table.
PubMed id: 39405360
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