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Lookup NU author(s): Dr Curtis Cottam, Dr Lauren Beck, Professor Christopher StewartORCiD, Dr Elisabeth Lowe, Dr James ConnollyORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© The Author(s) 2024. Virulence and metabolism are often interlinked to control the expression of essential colonisation factors in response to host-associated signals. Here, we identified an uncharacterised transporter of the dietary monosaccharide ʟ-arabinose that is widely encoded by the zoonotic pathogen enterohaemorrhagic Escherichia coli (EHEC), required for full competitive fitness in the mouse gut and highly expressed during human infection. Discovery of this transporter suggested that EHEC strains have an enhanced ability to scavenge ʟ-arabinose and therefore prompted us to investigate the impact of this nutrient on pathogenesis. Accordingly, we discovered that ʟ-arabinose enhances expression of the EHEC type 3 secretion system, increasing its ability to colonise host cells, and that the underlying mechanism is dependent on products of its catabolism rather than the sensing of ʟ-arabinose as a signal. Furthermore, using the murine pathogen Citrobacter rodentium, we show that ʟ-arabinose metabolism provides a fitness benefit during infection via virulence factor regulation, as opposed to supporting pathogen growth. Finally, we show that this mechanism is not restricted to ʟ-arabinose and extends to other pentose sugars with a similar metabolic fate. This work highlights the importance integrating central metabolism with virulence regulation in order to maximise competitive fitness of enteric pathogens within the host-niche.
Author(s): Cottam C, White RT, Beck LC, Stewart CJ, Beatson SA, Lowe EC, Grinter R, Connolly JPR
Publication type: Article
Publication status: Published
Journal: Nature Communications
Year: 2024
Volume: 15
Online publication date: 25/05/2024
Acceptance date: 16/05/2024
Date deposited: 11/06/2024
ISSN (electronic): 2041-1723
Publisher: Springer Nature
URL: https://doi.org/10.1038/s41467-024-48933-7
DOI: 10.1038/s41467-024-48933-7
Data Access Statement: The transcriptomic sequencing data is available from the NCBI Gene Expression Omnibus under the accession number GSE262155. The source data for Figs. 2–6, Supplementary Figs. 3–5 and 7–12 are provided as a Source Data file. Publicly available genome sequences were obtained from the NCBI Sequence Read Archive. Source data are provided with this paper.
PubMed id: 38796512
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