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Cited by 55Bacterial Genetics and BiotechnologyGut microbiota and healthDrug Transport and Resistance Mechanisms

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Outer membrane utilisomes mediate glycan uptake in gut Bacteroidetes

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White, Joshua B. R., Silale, Augustinas, Feasey, Matthew, Heunis, Tiaan, Zhu, Yiling, Zheng, Hong, Gajbhiye, Akshada, Firbank, Susan, Baslé, Arnaud, Trost, Matthias, Bolam, David N., van den Berg, Bert, Ranson, Neil A.·2023·Nature
DOI 10.1038/s41586-023-06146-wPMC PMC7618045

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Abstract

Abstract Bacteroidetes are abundant members of the human microbiota, with species occupying the distal gut capable of utilising a myriad of diet- and host-derived glycans. Transport of glycans across the outer membrane (OM) of these bacteria is mediated by SusCD protein complexes, comprising a membrane-embedded barrel and a lipoprotein lid, that are thought to operate via a ‘pedal-bin’ mechanism in which the lids open and close to facilitate substrate binding. However, additional cell surface-exposed lipoproteins, namely surface glycan binding proteins and glycoside hydrolases, play critical roles in the capture and processing of large glycan chains into transport-competent substrates. Despite constituting a crucial mechanism of nutrient acquisition by our colonic microbiota, the interactions between these components in the OM are poorly understood. Here we show that for the levan and dextran utilisation systems of Bacteroides thetaiotaomicron, the additional OM components assemble on the core SusCD transporter, forming stable glycan utilising machines which we term ‘utilisomes’. Single particle electron cryogenic electron microscopy (cryo-EM) structures in the absence and presence of substrate reveal concerted conformational changes that rationalise the role of each component for efficient nutrient capture, as well as providing a direct demonstration of the pedal bin mechanism of substrate capture in the intact utilisome.

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Metadata

Authors
White, J. B. R., Silale, A., Feasey, M., Heunis, T., Zhu, Y., Zheng, H., Gajbhiye, A., Firbank, S., Baslé, A., Trost, M., Bolam, D. N., van den Berg, B., & Ranson, N. A.
Affiliations
  • University of Leeds (GB)
  • Newcastle University (GB)
Corresponding author
  • van den Berg, Bert
  • Ranson, Neil A.
ORCID
Venue
Nature
Publisher
Springer Science and Business Media LLC
Published
2023-06-07
Volume
618
Issue
7965
Pages
583-589
ISSN
  • 0028-0836 (ISSN-L)
  • 1476-4687
DOI
10.1038/s41586-023-06146-w
PMC
PMC7618045
OpenAlex
W4379768254
Cited by
55
References
6
Citations by year
2026: 16 · 2025: 13 · 2024: 15 · 2023: 10
FWCI
8.96
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Research Explorer (The University of Manchester) (publishedVersion)
  • White Rose Research Online (University of Leeds, The University of Sheffield, University of York) (acceptedVersion, cc-by)
  • RePEc: Research Papers in Economics (submittedVersion)
Funders
  • Wellcome Trust (214222, 221524, 215064/Z/18/Z, 108466, 215064, 214222/Z/18/Z, /Z/15/Z, 221524/Z/20/Z, 108466/Z/15/Z)
  • Diamond Light Source (mx1221, mx13587, mx18598)
  • Newcastle University (mx18598)
  • University of Leeds (108466/Z/15/Z)
  • Biotechnology and Biological Sciences Research Council (REI20490)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
  • Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
Keywords
outer membrane, Bacteroides thetaiotaomicron, Bacteroidetes, glycan-binding proteins, glycoside hydrolases, colonic microbiota, nutrient acquisition, transporter conformational change, cryo-EM structure
MeSH terms
Bacteroides thetaiotaomicron, Bacterial Outer Membrane, Bacterial Outer Membrane Proteins, Glycoside Hydrolases, Humans, Polysaccharides, Gastrointestinal Tract

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