title: Characterization of glycosaminoglycan (GAG) sulfatases from the human gut symbiont Bacteroides thetaiotaomicron reveals the first GAG-specific bacterial endosulfatase.
abstract: 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.
authors.affiliation: From the Institut National de la Recherche Agronomique, ChemSyBio, UMR 1319 Micalis, F-78350 Jouy-en-Josas, France, the AgroParisTech, ChemSyBio, UMR 1319 Micalis, F-78350 Jouy-en-Josas, France.
authors.forename: Jonathan E
authors.initials: JE
authors.lastname: Ulmer
authors.affiliation: the Department of Chemistry and Biotechnology, Swedish University of Agricultural Sciences, P. O. Box 7015, SE-750 07 Uppsala, Sweden.
authors.forename: Eric Morssing
authors.initials: EM
authors.lastname: Vilén
authors.affiliation: the Department of Medical Biochemistry and Microbiology, Biomedical Center, Uppsala University, SE-751 23 Uppsala, Sweden.
authors.forename: Ramesh Babu
authors.initials: RB
authors.lastname: Namburi
authors.affiliation: From the Institut National de la Recherche Agronomique, ChemSyBio, UMR 1319 Micalis, F-78350 Jouy-en-Josas, France, the AgroParisTech, ChemSyBio, UMR 1319 Micalis, F-78350 Jouy-en-Josas, France.
authors.forename: Alhosna
authors.initials: A
authors.lastname: Benjdia
authors.affiliation: From the Institut National de la Recherche Agronomique, ChemSyBio, UMR 1319 Micalis, F-78350 Jouy-en-Josas, France, the AgroParisTech, ChemSyBio, UMR 1319 Micalis, F-78350 Jouy-en-Josas, France.
authors.forename: Julie
authors.initials: J
authors.lastname: Beneteau
authors.affiliation: the ICMMO/G2M/LCOM/UMR 8182(CNRS-UPS), LabEx LERMIT, Université Paris-Sud, 91405 Orsay Cedex, France, and.
authors.forename: Annie
authors.initials: A
authors.lastname: Malleron
authors.affiliation: the ICMMO/G2M/LCOM/UMR 8182(CNRS-UPS), LabEx LERMIT, Université Paris-Sud, 91405 Orsay Cedex, France, and.
authors.forename: David
authors.initials: D
authors.lastname: Bonnaffé
authors.affiliation: Sanofi R&D, Early to Candidate Unit, 195 Route d'Espagne, BP13669, 31036 Toulouse Cedex, France.
authors.forename: Pierre-Alexandre
authors.initials: PA
authors.lastname: Driguez
authors.affiliation: Sanofi R&D, Early to Candidate Unit, 195 Route d'Espagne, BP13669, 31036 Toulouse Cedex, France.
authors.forename: Karine
authors.initials: K
authors.lastname: Descroix
authors.affiliation: Sanofi R&D, Early to Candidate Unit, 195 Route d'Espagne, BP13669, 31036 Toulouse Cedex, France.
authors.forename: Gilbert
authors.initials: G
authors.lastname: Lassalle
authors.affiliation: the ICMMO/G2M/LCOM/UMR 8182(CNRS-UPS), LabEx LERMIT, Université Paris-Sud, 91405 Orsay Cedex, France, and.
authors.forename: Christine
authors.initials: C
authors.lastname: Le Narvor
authors.affiliation: the Department of Chemistry and Biotechnology, Swedish University of Agricultural Sciences, P. O. Box 7015, SE-750 07 Uppsala, Sweden.
authors.forename: Corine
authors.initials: C
authors.lastname: Sandström
authors.affiliation: the Department of Medical Biochemistry and Microbiology, Biomedical Center, Uppsala University, SE-751 23 Uppsala, Sweden, dorothe.spillmann@imbim.uu.se.
authors.forename: Dorothe
authors.initials: D
authors.lastname: Spillmann
authors.affiliation: From the Institut National de la Recherche Agronomique, ChemSyBio, UMR 1319 Micalis, F-78350 Jouy-en-Josas, France, the AgroParisTech, ChemSyBio, UMR 1319 Micalis, F-78350 Jouy-en-Josas, France, olivier.berteau@jouy.inra.fr.
authors.forename: Olivier
authors.initials: O
authors.lastname: Berteau
mesh_terms: D001439:Bacteroides / Q000201:enzymology*; D001483:Base Sequence; D002240:Carbohydrate Sequence; D017931:DNA Primers; D006025:Glycosaminoglycans / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008969:Molecular Sequence Data; D013429:Sulfatases / Q000378:metabolism*; D013559:Symbiosis
chemical_list: D017931:DNA Primers; D006025:Glycosaminoglycans; D013429:Sulfatases
keywords: Bacterial Metabolism; Bacteroides thetaiotaomicron; Chondroitin Sulfate; Enzyme Mechanism; Glycosaminoglycan; Heparan Sulfate; Microbiota; Sulfatase