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

Autor: Cottam C; Newcastle University Biosciences Institute, Newcastle University, NE2 4HH, Newcastle-upon-Tyne, UK., White RT; Institute of Environmental Science and Research, Wellington, New Zealand.; Australian Infectious Diseases Research Centre and School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, QLD, Australia., Beck LC; Newcastle University Translation and Clinical Research Institute, Newcastle University, NE2 4HH, Newcastle-upon-Tyne, UK., Stewart CJ; Newcastle University Translation and Clinical Research Institute, Newcastle University, NE2 4HH, Newcastle-upon-Tyne, UK., Beatson SA; Australian Infectious Diseases Research Centre and School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, QLD, Australia., Lowe EC; Newcastle University Biosciences Institute, Newcastle University, NE2 4HH, Newcastle-upon-Tyne, UK., Grinter R; Department of Microbiology, Biomedicine Discovery Institute, Monash University, Clayton, VIC, Australia., Connolly JPR; Newcastle University Biosciences Institute, Newcastle University, NE2 4HH, Newcastle-upon-Tyne, UK. James.Connolly2@newcastle.ac.uk.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2024 May 25; Vol. 15 (1), pp. 4462. Date of Electronic Publication: 2024 May 25.
DOI: 10.1038/s41467-024-48933-7
Abstrakt: 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.
(© 2024. The Author(s).)
Databáze: MEDLINE
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