How members of the human gut microbiota overcome the sulfation problem posed by glycosaminoglycans

Alan Cartmell, Elisabeth C. Lowe, Arnaud Baslé, Susan J. Firbank, Didier A. Ndeh, Heath Murray, Nicolas Terrapon, Vincent Lombard, Bernard Henrissat, Jeremy E. Turnbull, Mirjam Czjzek, Harry J. Gilbert, David N. Bolam

Research output: Contribution to journalArticlepeer-review

94 Citations (Scopus)
63 Downloads (Pure)


The human microbiota, which plays an important role in health and disease, uses complex carbohydrates as a major source of nutrients. Utilization hierarchy indicates that the host glycosaminoglycans heparin (Hep) and heparan sulfate (HS) are high-priority carbohydrates for Bacteroides thetaiotaomicron, a prominent member of the human microbiota. The sulfation patterns of these glycosaminoglycans are highly variable, which presents a significant enzymatic challenge to the polysaccharide lyases and sulfatases that mediate degradation. It is possible that the bacterium recruits lyases with highly plastic specificities and expresses a repertoire of enzymes that target substructures of the glycosaminoglycans with variable sulfation or that the glycans are desulfated before cleavage by the lyases. To distinguish between these mechanisms, the components of the B. thetaiotaomicron Hep/HS degrading apparatus were analyzed. The data showed that the bacterium expressed a single-surface endo-acting lyase that cleaved HS, reflecting its higher molecular weight compared with Hep. Both Hep and HS oligosaccharides imported into the periplasm were degraded by a repertoire of lyases, with each enzyme displaying specificity for substructures within these glycosaminoglycans that display a different degree of sulfation. Furthermore, the crystal structures of a key surface glycan binding protein, which is able to bind both Hep and HS, and periplasmic sulfatases reveal the major specificity determinants for these proteins. The locus described here is highly conserved within the human gut Bacteroides, indicating that the model developed is of generic relevance to this important microbial community.

Original languageEnglish
Pages (from-to)7037-7042
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number27
Early online date19 Jun 2017
Publication statusPublished - 3 Jul 2017


  • Bacteroides thetaiotaomicron
  • Glycosaminoglycan degradation
  • Heparan sulfate
  • Heparin
  • Human gut microbiota

ASJC Scopus subject areas

  • General


Dive into the research topics of 'How members of the human gut microbiota overcome the sulfation problem posed by glycosaminoglycans'. Together they form a unique fingerprint.

Cite this