Metabolism of multiple glycosaminoglycans by Bacteroides thetaiotaomicron is orchestrated by a versatile core genetic locus.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
31 01 2020
31 01 2020
Historique:
received:
09
07
2019
accepted:
10
01
2020
entrez:
2
2
2020
pubmed:
2
2
2020
medline:
12
5
2020
Statut:
epublish
Résumé
The human gut microbiota (HGM), which is critical to human health, utilises complex glycans as its major carbon source. Glycosaminoglycans represent an important, high priority, nutrient source for the HGM. Pathways for the metabolism of various glycosaminoglycan substrates remain ill-defined. Here we perform a biochemical, genetic and structural dissection of the genetic loci that orchestrates glycosaminoglycan metabolism in the organism Bacteroides thetaiotaomicron. Here, we report: the discovery of two previously unknown surface glycan binding proteins which facilitate glycosaminoglycan import into the periplasm; distinct kinetic and genetic specificities of various periplasmic lyases which dictate glycosaminoglycan metabolic pathways; understanding of endo sulfatase activity questioning the paradigm of how the 'sulfation problem' is handled by the HGM; and 3D crystal structures of the polysaccharide utilisation loci encoded sulfatases. Together with comparative genomic studies, our study fills major gaps in our knowledge of glycosaminoglycan metabolism by the HGM.
Identifiants
pubmed: 32005816
doi: 10.1038/s41467-020-14509-4
pii: 10.1038/s41467-020-14509-4
pmc: PMC6994673
doi:
Substances chimiques
Bacterial Proteins
0
Glycosaminoglycans
0
Polysaccharides
0
Sulfatases
EC 3.1.6.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
646Subventions
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : Medical Research Council
Pays : United Kingdom
Commentaires et corrections
Type : ErratumIn
Références
Mohajeri, M. H. et al. The role of the microbiome for human health: from basic science to clinical applications. Eur. J. Nutr. 57, 1–14 (2018).
pubmed: 5962619
pmcid: 5962619
Koropatkin, N. M., Cameron, E. A. & Martens, E. C. How glycan metabolism shapes the human gut microbiota. Nat. Rev. Microbiol. 10, 323–335 (2012).
pubmed: 22491358
pmcid: 4005082
Sweeney, T. E. & Morton, J. M. The human gut microbiome: a review of the effect of obesity and surgically induced weight loss. JAMA Surg. 148, 563–569 (2013).
pubmed: 4392891
pmcid: 4392891
Martens, E. C. et al. Recognition and degradation of plant cell wall polysaccharides by two human gut symbionts. PLoS Biol. 9, e1001221 (2011).
pubmed: 3243724
pmcid: 3243724
Lapebie, P., Lombard, V., Drula, E., Terrapon, N. & Henrissat, B. Bacteroidetes use thousands of enzyme combinations to break down glycans. Nat. Commun. 10, 2043 (2019).
pubmed: 6499787
pmcid: 6499787
Cartmell, A. et al. A surface endogalactanase in Bacteroides thetaiotaomicron confers keystone status for arabinogalactan degradation. Nat. Microbiol. 3, 1314–1326 (2018).
pubmed: 6217937
pmcid: 6217937
Larsbrink, J. et al. A discrete genetic locus confers xyloglucan metabolism in select human gut Bacteroidetes. Nature 506, 498–502 (2014).
pubmed: 24463512
pmcid: 24463512
Luis, A. S. et al. Dietary pectic glycans are degraded by coordinated enzyme pathways in human colonic Bacteroides. Nat. Microbiol. 3, 210–219 (2018).
pubmed: 29255254
pmcid: 29255254
Ndeh, D. et al. Complex pectin metabolism by gut bacteria reveals novel catalytic functions. Nature 544, 65–70 (2017).
pubmed: 28329766
pmcid: 28329766
Pudlo, N. A. et al. Symbiotic human gut bacteria with variable metabolic priorities for host mucosal glycans. mBio 6, e01282–01215 (2015).
pubmed: 4659458
pmcid: 4659458
Rogers, T. E. et al. Dynamic responses of Bacteroides thetaiotaomicron during growth on glycan mixtures. Mol. Microbiol. 88, 876–890 (2013).
pubmed: 3700664
pmcid: 3700664
Tuncil, Y. E. et al. Reciprocal prioritization to dietary glycans by gut bacteria in a competitive environment promotes stable coexistence. mBio 8, e01068–17 (2017).
pubmed: 5635687
pmcid: 5635687
Raghavan, V., Lowe, E. C., Townsend, G. E. 2nd, Bolam, D. N. & Groisman, E. A. Tuning transcription of nutrient utilization genes to catabolic rate promotes growth in a gut bacterium. Mol. Microbiol. 93, 1010–1025 (2014).
Salyers, A. A. & O’Brien, M. Cellular location of enzymes involved in chondroitin sulfate breakdown by Bacteroides thetaiotaomicron. J. Bacteriol. 143, 772–780 (1980).
pubmed: 294361
pmcid: 294361
Shaya, D. et al. Composite active site of chondroitin lyase ABC accepting both epimers of uronic acid. Glycobiology 18, 270–277 (2008).
Helbert, W. et al. Discovery of novel carbohydrate-active enzymes through the rational exploration of the protein sequences space. Proc. Natl Acad. Sci. USA 116, 6063–6068 (2019).
pubmed: 30850540
pmcid: 30850540
Hickey, C. A. et al. Colitogenic Bacteroides thetaiotaomicron antigens access host immune cells in a sulfatase-dependent manner via outer membrane vesicles. Cell Host Microbe 17, 672–680 (2015).
pubmed: 25974305
pmcid: 25974305
Ndeh, D. et al. The human gut microbe Bacteroides thetaiotaomicron encodes the founding member of a novel glycosaminoglycan-degrading polysaccharide lyase family PL29. J. Biol. Chem. 293, 17906–17916 (2018).
pubmed: 30262663
pmcid: 30262663
Barbeyron, T. et al. Matching the diversity of sulfated biomolecules: creation of a classification database for sulfatases reflecting their substrate specificity. PloS ONE 11, e0164846 (2016).
pubmed: 27749924
pmcid: 27749924
Ulmer, J. E. et al. Characterization of glycosaminoglycan (GAG) sulfatases from the human gut symbiont Bacteroides thetaiotaomicron reveals the first GAG-specific bacterial endosulfatase. J. Biol. Chem. 289, 24289–24303 (2014).
pubmed: 25002587
pmcid: 25002587
Hanson, S. R., Best, M. D. & Wong, C. H. Sulfatases: structure, mechanism, biological activity, inhibition, and synthetic utility. Angew. Chem. 43, 5736–5763 (2004).
Hettle, A. G. et al. The molecular basis of polysaccharide sulfatase activity and a nomenclature for catalytic subsites in this class of enzyme. Structure 26, 747–758 e744 (2018).
pubmed: 29681469
pmcid: 29681469
Konasani, V. R., Jin, C., Karlsson, N. G. & Albers, E. A novel ulvan lyase family with broad-spectrum activity from the ulvan utilisation loci of Formosa agariphila KMM 3901. Sci. Rep. 8, 14713 (2018).
pubmed: 30279430
pmcid: 30279430
Cartmell, A. et al. How members of the human gut microbiota overcome the sulfation problem posed by glycosaminoglycans. Proc. Natl Acad. Sci. USA 114, 7037–7042 (2017).
pubmed: 28630303
pmcid: 28630303
Maruyama, Y. et al. Metabolic fate of unsaturated glucuronic/iduronic acids from glycosaminoglycans: molecular identification and structure determination of streptococcal isomerase and dehydrogenase. J. Biol. Chem. 290, 6281–6292 (2015).
pubmed: 25605731
pmcid: 25605731
Raghavan, V. & Groisman, E. A. Species-specific dynamic responses of gut bacteria to a mammalian glycan. J. Bacteriol. 197, 1538–1548 (2015).
pubmed: 25691527
pmcid: 25691527
Goodman, A. L. et al. Identifying genetic determinants needed to establish a human gut symbiont in its habitat. Cell Host Microbe 6, 279–289 (2009).
pubmed: 19748469
pmcid: 2895552
Rubinstein, A., Nakar, D. & Sintov, A. Colonic drug delivery: enhanced release of indomethacin from cross-linked chondroitin matrix in rat cecal content. Pharm. Res. 9, 276–278 (1992).
pubmed: 1553354
pmcid: 1553354
Martens, E. C., Chiang, H. C. & Gordon, J. I. Mucosal glycan foraging enhances fitness and transmission of a saccharolytic human gut bacterial symbiont. Cell Host Microbe 4, 447–457 (2008).
pubmed: 18996345
pmcid: 18996345
Koropatkin, N. M., Martens, E. C., Gordon, J. I. & Smith, T. J. Starch catabolism by a prominent human gut symbiont is directed by the recognition of amylose helices. Structure 16, 1105–1115 (2008).
pubmed: 2563962
pmcid: 2563962
Schindelin, J. et al. Fiji: an open-source platform for biological-image analysis. Nat. Methods 9, 676–682 (2012).
pubmed: 22743772
pmcid: 22743772
Drummond, K. J., Yates, E. A. & Turnbull, J. E. Electrophoretic sequencing of heparin/heparan sulfate oligosaccharides using a highly sensitive fluorescent end label. Proteomics 1, 304–310 (2001).
Kabsch, W. XDS. Acta Crystallogr. Sect. D. Biol. Crystallogr. 66, 125–132 (2010).
Evans, P. Scaling and assessment of data quality. Acta Crystallogr. Sect. D. Biol. Crystallogr. 62, 72–82 (2006).
Evans, P. R. An introduction to data reduction: space-group determination, scaling and intensity statistics. Acta Crystallogr. Sect. D. Biol. Crystallogr. 67, 282–292 (2011).
Long, F., Vagin, A. A., Young, P. & Murshudov, G. N. BALBES: a molecular-replacement pipeline. Acta Crystallogr. Sect. D. Biol. Crystallogr. 64, 125–132 (2008).
Vagin, A. & Teplyakov, A. Molecular replacement with MOLREP. Acta Crystallogr. Sect. D. Biol. Crystallogr. 66, 22–25 (2010).
Emsley, P., Lohkamp, B., Scott, W. G. & Cowtan, K. Features and development of Coot. Acta Crystallogr. Sect. D. Biol. Crystallogr. 66, 486–501 (2010).
Murshudov, G. N. et al. REFMAC5 for the refinement of macromolecular crystal structures. Acta Crystallogr. Sect. D. Biol. Crystallogr. 67, 355–367 (2011).
Chen, V. B. et al. MolProbity: all-atom structure validation for macromolecular crystallography. Acta Crystallogr. Sect. D. Biol. Crystallogr. 66, 12–21 (2010).
Collaborative Computational Project, N. The CCP4 suite: programs for protein crystallography. Acta Crystallogr. Sect. D. Biol. Crystallogr. 50, 760–763 (1994).