Unravelling the specificity and mechanism of sialic acid recognition by the gut symbiont Ruminococcus gnavus

C. David Owen, Louise E. Tailford, Serena Monaco, Tanja Šuligoj, Laura Vaux, Romane Lallement, Zahra Khedri, Hai Yu, Karine Lecointe, John Walshaw, Sandra Tribolo, Marc Horrex, Andrew Bell, Xi Chen, Gary L. Taylor, Ajit Varki, Jesus Angulo, Nathalie Juge

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

Ruminococcus gnavus is a human gut symbiont wherein the ability to degrade mucins is mediated by an intramolecular trans-sialidase (RgNanH). RgNanH comprises a GH33 catalytic domain and a sialic acid-binding carbohydrate-binding module (CBM40). Here we used glycan arrays, STD NMR, X-ray crystallography, mutagenesis and binding assays to determine the structure and function of RgNanH-CBM40 (RgCBM40). RgCBM40 displays the canonical CBM40 β-sandwich fold and broad specificity towards sialoglycans with millimolar binding affinity towards α2,3- or α2,6-sialyllactose. RgCBM40 binds to mucus produced by goblet cells and to purified mucins, providing direct evidence for a CBM40 as a novel bacterial mucus adhesin. Bioinformatics data show that RgCBM40 canonical type domains are widespread among Firmicutes. Furthermore, binding of R. gnavus ATCC 29149 to intestinal mucus is sialic acid mediated. Together, this study reveals novel features of CBMs which may contribute to the biogeography of symbiotic bacteria in the gut.

Original languageEnglish (US)
Article number2196
JournalNature Communications
Volume8
Issue number1
DOIs
StatePublished - Dec 1 2017

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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    Owen, C. D., Tailford, L. E., Monaco, S., Šuligoj, T., Vaux, L., Lallement, R., Khedri, Z., Yu, H., Lecointe, K., Walshaw, J., Tribolo, S., Horrex, M., Bell, A., Chen, X., Taylor, G. L., Varki, A., Angulo, J., & Juge, N. (2017). Unravelling the specificity and mechanism of sialic acid recognition by the gut symbiont Ruminococcus gnavus. Nature Communications, 8(1), [2196]. https://doi.org/10.1038/s41467-017-02109-8