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NJ, HW, DN, AMG received funding from InnovateUK Biocatalyst grant Glycoenzymes for Bioindustries (grant BB/M029042/). NJ, EHC,DL received funding from Biotechnology and Biological Sciences Research Council (BBSRC) Institute Strategic Programme Gut Microbes and Health (grant BB/R012490/1). JA and SM acknowledge support of BBSRC (grant BB/ P010660/1). JA was also supported by the Spanish Ministry of Science, Innovation and Universities through the grant PID2019-109395GB-I00. TH, RSR, SW were funded by BBSRC Norwich Research Park Doctoral Training Grant BB/ M011216/. WB was funded the European Unions Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No 814102. We acknowledge the participation of the Protein-Glycan Interaction Resource of the Consortium for Functional Glycomics (supporting grant R24 GM098791) and the National Center for Functional Glycomics (NCFG) at Beth Israel Deaconess Medical Center, Harvard Medical School (supporting grant P41 GM10369). We acknowledge George Savva (Quadram Institute Bioscience) supported by the BBSRC Core Capability Grant BB/CCG1860/1 for help with statistical analyses of growth assays. We would like to thank Diamond Light Source beamlines VMXi, I24, I03 and I04 for beamtime and assistance, as well as the crystallisation facility at Harwell for access and support. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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Sánchez Salom, LauraAuthor

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December 6, 2024
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The human gut symbiont Ruminococcus gnavus shows specificity to blood group A antigen during mucin glycan foraging: Implication for niche colonisation in the gastrointestinal tract

Publicated to:Plos Biology. 19 (12): e3001498- - 2021-12-01 19(12), DOI: 10.1371/journal.pbio.3001498

Authors: Wu, Haiyang; Crost, Emmanuelle H; Owen, C David; van Bakel, Wouter; Martinez Gascuena, Ana; Latousakis, Dimitrios; Hicks, Thomas; Walpole, Samuel; Urbanowicz, Paulina A; Ndeh, Didier; Monaco, Serena; Sanchez Salom, Laura; Griffiths, Ryan; Reynolds, Raven S; Colvile, Anna; Spencer, Daniel I R; Walsh, Martin; Angulo, Jesus; Juge, Nathalie

Affiliations

Diamond Light Source Ltd, Didcot, Oxon, England - Author
Inst Biol & Med Engn, Guangzhou, Peoples R China - Author
Inst Invest Quim, Seville, Spain - Author
John Innes Ctr, Norwich, Norfolk, England - Author
Ludger Ltd, Abingdon, Oxon, England - Author
Quadram Inst Biosci, Norwich, Norfolk, England - Author
Res Complex Harwell, Didcot, Oxon, England - Author
Univ Dundee, Dundee, Scotland - Author
Univ East Anglia, Norwich, Norfolk, England - Author
Univ Seville, Seville, Spain - Author
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Abstract

The human gut symbiont Ruminococcus gnavus displays strain-specific repertoires of glycoside hydrolases (GHs) contributing to its spatial location in the gut. Sequence similarity network analysis identified strain-specific differences in blood-group endo-beta-1,4-galactosidase belonging to the GH98 family. We determined the substrate and linkage specificities of GH98 from R. gnavus ATCC 29149, RgGH98, against a range of defined oligosaccharides and glycoconjugates including mucin. We showed by HPAEC-PAD and LC-FD-MS/MS that RgGH98 is specific for blood group A tetrasaccharide type II (BgA II). Isothermal titration calorimetry (ITC) and saturation transfer difference (STD) NMR confirmed RgGH98 affinity for blood group A over blood group B and H antigens. The molecular basis of RgGH98 strict specificity was further investigated using a combination of glycan microarrays, site-directed mutagenesis, and X-ray crystallography. The crystal structures of RgGH98 in complex with BgA trisaccharide (BgAtri) and of RgGH98 E411A with BgA II revealed a dedicated hydrogen network of residues, which were shown by site-directed mutagenesis to be critical to the recognition of the BgA epitope. We demonstrated experimentally that RgGH98 is part of an operon of 10 genes that is overexpresssed in vitro when R. gnavus ATCC 29149 is grown on mucin as sole carbon source as shown by RNAseq analysis and RT-qPCR confirmed RgGH98 expression on BgA II growth. Using MALDI-ToF MS, we showed that RgGH98 releases BgAtri from mucin and that pretreatment of mucin with RgGH98 confered R. gnavus E1 the ability to grow, by enabling the E1 strain to metabolise BgAtri and access the underlying mucin glycan chain. These data further support that the GH repertoire of R. gnavus strains enable them to colonise different nutritional niches in the human gut and has potential applications in diagnostic and therapeutics against infection.

Keywords

Abo blood-group systemBindingBlood group antigensClostridialesComplexEndo-beta-galactosidaseGastrointestinal microbiomeGastrointestinal tractGenGlycoside hydrolaseGlycoside hydrolasesHumansMuc1 protein, humanMucin-1MucinsMucusO-glycosylationOligosaccharidesPolysaccharidesRuminococcusSearchSoftwareSubstrate specificityTandem mass spectrometry

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal Plos Biology due to its progression and the good impact it has achieved in recent years, according to the agency WoS (JCR), it has become a reference in its field. In the year of publication of the work, 2021, it was in position 6/94, thus managing to position itself as a Q1 (Primer Cuartil), in the category Biology. Notably, the journal is positioned above the 90th percentile.

From a relative perspective, and based on the normalized impact indicator calculated from the Field Citation Ratio (FCR) of the Dimensions source, it yields a value of: 3.1, which indicates that, compared to works in the same discipline and in the same year of publication, it ranks as a work cited above average. (source consulted: Dimensions Jul 2025)

Specifically, and according to different indexing agencies, this work has accumulated citations as of 2025-07-04, the following number of citations:

  • WoS: 15
  • Europe PMC: 11

Impact and social visibility

From the perspective of influence or social adoption, and based on metrics associated with mentions and interactions provided by agencies specializing in calculating the so-called "Alternative or Social Metrics," we can highlight as of 2025-07-04:

  • The use, from an academic perspective evidenced by the Altmetric agency indicator referring to aggregations made by the personal bibliographic manager Mendeley, gives us a total of: 37.
  • The use of this contribution in bookmarks, code forks, additions to favorite lists for recurrent reading, as well as general views, indicates that someone is using the publication as a basis for their current work. This may be a notable indicator of future more formal and academic citations. This claim is supported by the result of the "Capture" indicator, which yields a total of: 36 (PlumX).

With a more dissemination-oriented intent and targeting more general audiences, we can observe other more global scores such as:

  • The Total Score from Altmetric: 41.15.
  • The number of mentions on the social network Facebook: 1 (Altmetric).
  • The number of mentions on the social network X (formerly Twitter): 24 (Altmetric).
  • The number of mentions in news outlets: 4 (Altmetric).

It is essential to present evidence supporting full alignment with institutional principles and guidelines on Open Science and the Conservation and Dissemination of Intellectual Heritage. A clear example of this is:

  • The work has been submitted to a journal whose editorial policy allows open Open Access publication.

Leadership analysis of institutional authors

This work has been carried out with international collaboration, specifically with researchers from: China; United Kingdom.