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Characterization of Glycosaminoglycan (GAG) Sulfatases from the Human Gut Symbiont Bacteroides thetaiotaomicron Reveals the First GAG-specific Bacterial Endosulfatase
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
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2014 (English)In: Journal of Biological Chemistry, ISSN 0021-9258, E-ISSN 1083-351X, Vol. 289, no 35, 24289-24303 p.Article in journal (Refereed) Published
Abstract [en]

Background: Sulfatases are emerging as key adaptive tools of commensal bacteria to their host. Results: The first bacterial endo-O-sulfatase and three exo-O-sulfatases from the human commensal Bacteroides thetaiotaomicron, specific for glycosaminoglycans, have been discovered and characterized. Conclusion: Commensal bacteria possess a unique array of highly specific sulfatases to metabolize host glycans. Significance: Bacterial sulfatases are much more diverse than anticipated. Despite the importance of the microbiota in human physiology, the molecular bases that govern the interactions between these commensal bacteria and their host remain poorly understood. We recently reported that sulfatases play a key role in the adaptation of a major human commensal bacterium, Bacteroides thetaiotaomicron, to its host (Benjdia, A., Martens, E. C., Gordon, J. I., and Berteau, O. (2011) J. Biol. Chem. 286, 25973-25982). We hypothesized that sulfatases are instrumental for this bacterium, and related Bacteroides species, to metabolize highly sulfated glycans (i.e. mucins and glycosaminoglycans (GAGs)) and to colonize the intestinal mucosal layer. Based on our previous study, we investigated 10 sulfatase genes induced in the presence of host glycans. Biochemical characterization of these potential sulfatases allowed the identification of GAG-specific sulfatases selective for the type of saccharide residue and the attachment position of the sulfate group. Although some GAG-specific bacterial sulfatase activities have been described in the literature, we report here for the first time the identity and the biochemical characterization of four GAG-specific sulfatases. Furthermore, contrary to the current paradigm, we discovered that B. thetaiotaomicron possesses an authentic GAG endosulfatase that is active at the polymer level. This type of sulfatase is the first one to be identified in a bacterium. Our study thus demonstrates that bacteria have evolved more sophisticated and diverse GAG sulfatases than anticipated and establishes how B. thetaiotaomicron, and other major human commensal bacteria, can metabolize and potentially tailor complex host glycans.

Place, publisher, year, edition, pages
2014. Vol. 289, no 35, 24289-24303 p.
Keyword [en]
Bacterial Metabolism, Chondroitin Sulfate, Enzyme Mechanism, Glycosaminoglycan, Heparan Sulfate, Bacteroides thetaiotaomicron, Microbiota, Sulfatase
National Category
Biochemistry and Molecular Biology
URN: urn:nbn:se:uu:diva-233581DOI: 10.1074/jbc.M114.573303ISI: 000341505600025OAI: oai:DiVA.org:uu-233581DiVA: diva2:754957

Delad första författare för Namburi

Delad sista författare för Spillmann

Available from: 2014-10-13 Created: 2014-10-07 Last updated: 2016-02-12Bibliographically approved
In thesis
1. Brittlestars Galactosaminoglycans and Tools to Study their Structure
Open this publication in new window or tab >>Brittlestars Galactosaminoglycans and Tools to Study their Structure
2016 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

In all living organisms, biological activities such as proper functioning and co-ordination of different organs will depend on different cells and molecular interactions. In some organisms the loss of functional organs or damage of organs can be lethal, whereas in others a special process called regeneration can retrieve lost organs. The molecular details of regeneration are still not completely understood in many organisms. Echinoderms are close to vertebrates in the evolutionary tree and are well known for their amazing regeneration capacity. So we chose to investigate the molecular processes of regeneration mechanism with an interest towards our favorite groups of molecules, glycosaminoglycans (GAGs). GAGs are linear polysaccharides, expressed on all cell surfaces and extracellular space and are also known to be involved in many cellular activities. We aimed to characterize the GAGs present in Echinodermata species Amphiura filiformis and investigated their role during arm regeneration.

In Paper I we characterized the structure and function of GAGs from A. filiformis and identified that A. filiformis contains CS/DS type of GAGs, but no HS. The sulfation degree of these CS/DS is close to the one of heparin, i.e. they are highly sulfated. These chains are able to bind FGF-2 growth factor and induce FGF-2 mediated cell signaling. In Paper II we further characterized these GAGs for their localization and for their role in arm regeneration in A. filiformis. Immuno- and histochemical stainings on arm sections revealed that CS/DS GAGs are localized around the podia, surrounding the water vascular system, and around the muscle tissues. Inhibition of sulfated GAG biosynthesis by chlorate treatment affected the regeneration efficiency of the arms, which may be an indication of the importance of CS/DS structures in A. filiformis arm regeneration. We also characterized some bacterial sulfatases in Paper III and a lyase in Paper IV from human and canine gut symbiotic bacteria. Here we sought to find the substrate specificity and optimal conditions for these enzymes’ activities. Our findings suggest that these polysaccharide lyase and sulfatases can be used as potential tools to characterize different GAG structures and their application could further add knowledge on diseases mechanisms related to host pathogen interactions.




Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2016. 63 p.
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1172
Chondroitin sulfate, Brittlestars, Gut bacteria, H. bizzozeronii, B.thetaiotaomicron
National Category
Microbiology in the medical area Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy) Cell and Molecular Biology
Research subject
Biochemistry; Microbiology; Molecular Biology
urn:nbn:se:uu:diva-271559 (URN)978-91-554-9449-0 (ISBN)
Public defence
2016-02-26, A1: 107, BMC, Husargatan 3, Uppsala, 09:15 (English)
Available from: 2016-02-02 Created: 2016-01-10 Last updated: 2016-02-12

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Namburi, Ramesh BabuSpillmann, Dorothe
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