Toggle Main Menu Toggle Search

Open Access padlockePrints

Metabolism of l-arabinose converges with virulence regulation to promote enteric pathogen fitness

Lookup NU author(s): Dr Curtis Cottam, Dr Lauren Beck, Professor Christopher StewartORCiD, Dr Elisabeth Lowe, Dr James ConnollyORCiD

Downloads


Licence

This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

© 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.


Publication metadata

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


Altmetrics

Altmetrics provided by Altmetric


Funding

Funder referenceFunder name
226644/Z/22/Z
Barbour Foundation
Faculty Fellowship (Newcastle University)
MR/X007197/1
RGS\R2\202100
SBF005\1029
Springboard Award, Academy of Medical Sciences/Wellcome Trust
Royal Society Research Grant

Share