Elucidation of a sialic acid metabolism pathway in mucus-foraging Ruminococcus gnavus unravels mechanisms of bacterial adaptation to the gut

Bell, Andrew, Brunt, Jason ORCID: https://orcid.org/0000-0002-7815-2165, Crost, Emmanuelle, Vaux, Laura, Nepravishta, Ridvan, Owen, C. David, Latousakis, Dimitrios, Xiao, An, Li, Wanqing, Chen, Xi, Walsh, Martin A., Claesen, Jan, Angulo, Jesus ORCID: https://orcid.org/0000-0001-7250-5639, Thomas, Gavin H. and Juge, Nathalie (2019) Elucidation of a sialic acid metabolism pathway in mucus-foraging Ruminococcus gnavus unravels mechanisms of bacterial adaptation to the gut. Nature Microbiology, 4. 2393–2404. ISSN 2058-5276

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Abstract

Sialic acid (N-acetylneuraminic acid (Neu5Ac)) is commonly found in the terminal location of colonic mucin glycans where it is a much-coveted nutrient for gut bacteria, including Ruminococcus gnavus. R. gnavus is part of the healthy gut microbiota in humans, but it is disproportionately represented in diseases. There is therefore a need to understand the molecular mechanisms that underpin the adaptation of R. gnavus to the gut. Previous in vitro research has demonstrated that the mucin-glycan-foraging strategy of R. gnavus is strain dependent and is associated with the expression of an intramolecular trans-sialidase, which releases 2,7-anhydro-Neu5Ac, rather than Neu5Ac, from mucins. Here, we unravelled the metabolism pathway of 2,7-anhydro-Neu5Ac in R. gnavus that is underpinned by the exquisite specificity of the sialic transporter for 2,7-anhydro-Neu5Ac and by the action of an oxidoreductase that converts 2,7-anhydro-Neu5Ac into Neu5Ac, which then becomes a substrate of a Neu5Ac-specific aldolase. Having generated an R. gnavus nan-cluster deletion mutant that lost the ability to grow on sialylated substrates, we showed that—in gnotobiotic mice colonized with R. gnavus wild-type (WT) and mutant strains—the fitness of the nan mutant was significantly impaired, with a reduced ability to colonize the mucus layer. Overall, we revealed a unique sialic acid pathway in bacteria that has important implications for the spatial adaptation of mucin-foraging gut symbionts in health and disease.

Item Type: Article
Faculty \ School: Faculty of Science > School of Biological Sciences
Faculty of Medicine and Health Sciences > Norwich Medical School
Faculty of Science > School of Pharmacy
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Depositing User: LivePure Connector
Date Deposited: 19 Dec 2022 16:33
Last Modified: 19 Dec 2022 16:33
URI: https://ueaeprints.uea.ac.uk/id/eprint/90305
DOI: 10.1038/s41564-019-0590-7

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