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      Glycan complexity dictates microbial resource allocation in the large intestine

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          Abstract

          The structure of the human gut microbiota is controlled primarily through the degradation of complex dietary carbohydrates, but the extent to which carbohydrate breakdown products are shared between members of the microbiota is unclear. We show here, using xylan as a model, that sharing the breakdown products of complex carbohydrates by key members of the microbiota, such as Bacteroides ovatus, is dependent on the complexity of the target glycan. Characterization of the extensive xylan degrading apparatus expressed by B. ovatus reveals that the breakdown of the polysaccharide by the human gut microbiota is significantly more complex than previous models suggested, which were based on the deconstruction of xylans containing limited monosaccharide side chains. Our report presents a highly complex and dynamic xylan degrading apparatus that is fine-tuned to recognize the different forms of the polysaccharide presented to the human gut microbiota.

          Abstract

          The human gut microbiota helps us to degrade complex dietary carbohydrates such as xylan and, in turn, the carbohydrate breakdown products control the structure of the microbiota. Here the authors characterize the xylan-degrading apparatus of a key member of the gut microbiota, Bacteroides ovatus.

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          Most cited references43

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          REFMAC5 dictionary: organization of prior chemical knowledge and guidelines for its use.

          One of the most important aspects of macromolecular structure refinement is the use of prior chemical knowledge. Bond lengths, bond angles and other chemical properties are used in restrained refinement as subsidiary conditions. This contribution describes the organization and some aspects of the use of the flexible and human/machine-readable dictionary of prior chemical knowledge used by the maximum-likelihood macromolecular-refinement program REFMAC5. The dictionary stores information about monomers which represent the constitutive building blocks of biological macromolecules (amino acids, nucleic acids and saccharides) and about numerous organic/inorganic compounds commonly found in macromolecular crystallography. It also describes the modifications the building blocks undergo as a result of chemical reactions and the links required for polymer formation. More than 2000 monomer entries, 100 modification entries and 200 link entries are currently available. Algorithms and tools for updating and adding new entries to the dictionary have also been developed and are presented here. In many cases, the REFMAC5 dictionary allows entirely automatic generation of restraints within REFMAC5 refinement runs.
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            Mucosal glycan foraging enhances fitness and transmission of a saccharolytic human gut bacterial symbiont.

            The distal human gut is a microbial bioreactor that digests complex carbohydrates. The strategies evolved by gut microbes to sense and process diverse glycans have important implications for the assembly and operation of this ecosystem. The human gut-derived bacterium Bacteroides thetaiotaomicron forages on both host and dietary glycans. Its ability to target these substrates resides in 88 polysaccharide utilization loci (PULs), encompassing 18% of its genome. Whole genome transcriptional profiling and genetic tests were used to define the mechanisms underlying host glycan foraging in vivo and in vitro. PULs that target all major classes of host glycans were identified. However, mucin O-glycans are the principal host substrate foraged in vivo. Simultaneous deletion of five genes encoding ECF-sigma transcription factors, which activate mucin O-glycan utilization, produces defects in bacterial persistence in the gut and in mother-to-offspring transmission. Thus, PUL-mediated glycan catabolism is an important component in gut colonization and may impact microbiota ecology.
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              Complex Glycan Catabolism by the Human Gut Microbiota: The Bacteroidetes Sus-like Paradigm*

              Trillions of microbes inhabit the distal gut of adult humans. They have evolved to compete efficiently for nutrients, including a wide array of chemically diverse, complex glycans present in our diets, secreted by our intestinal mucosa, and displayed on the surfaces of other gut microbes. Here, we review how members of the Bacteroidetes, one of two dominant gut-associated bacterial phyla, process complex glycans using a series of similarly patterned, cell envelope-associated multiprotein systems. These systems provide insights into how gut, as well as terrestrial and aquatic, Bacteroidetes survive in highly competitive ecosystems.
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                Author and article information

                Journal
                Nat Commun
                Nat Commun
                Nature Communications
                Nature Pub. Group
                2041-1723
                26 June 2015
                2015
                : 6
                : 7481
                Affiliations
                [1 ]Institute for Cell and Molecular Biosciences, The Medical School, Newcastle University , Newcastle upon Tyne NE2 4HH, UK
                [2 ]Department of Biochemistry, University of Cambridge , Tennis Court Road, Cambridge CB2 1QW, UK
                [3 ]Architecture et Fonction des Macromolécules Biologiques (AFMB) , UMR 7257 CNRS, Université Aix-Marseille, 163 Avenue de Luminy, 13288 Marseille, France
                [4 ]Department of Microbiology and Immunology, University of Michigan Medical School , Ann Arbor, Michigan 48109, USA
                [5 ]United States Department of Agriculture- Agricultural Research Service, Eastern Regional Research Center , 600 East Mermaid Lane, Wyndmoor, Pennsylvania 19038, USA
                [6 ]Department of Biological Sciences, King Abdulaziz University , Jeddah, Saudi Arabia
                Author notes
                [*]

                These authors contributed equally to this work.

                Article
                ncomms8481
                10.1038/ncomms8481
                4491172
                26112186
                706e37e4-f11e-4fd0-96ac-133ff15092bd
                Copyright © 2015, Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved.

                This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

                History
                : 11 November 2014
                : 13 May 2015
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