Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Mucosal Glycan Foraging Enhances the Fitness and Transmission of a Saccharolytic Human Distal Gut Symbiont

ABSTRACT: Gene expression profiles of Bacteroides thetaiotaomicron in vitro during growth on host mucosal polysaccharides as sole carbon sources. All substrates in this series are derived from porcine gastric mucin and include mucin O-glycans and glycosaminoglycans. Two different culture formats used: 800ml batch-culture bioreactors and 5ml tube cultures (format is indicated within each sample title). Each set of growths was referenced to a minimal medium glucose reference corressponding to the same culture format. Unfractionated porcine mucosal glycan (PMG) growths were compared to previously published in vivo datasets, which were referenced to the 800ml minimal medium glucose reference dataset.

ORGANISM(S): Bacteroides thetaiotaomicron

SUBMITTER: Eric Martens

PROVIDER: E-GEOD-11944 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Mucosal glycan foraging enhances fitness and transmission of a saccharolytic human gut bacterial symbiont.

Martens Eric C EC Chiang Herbert C HC Gordon Jeffrey I JI

Cell host & microbe 20081101 5

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 profil ...[more]

PMID: 18996345

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Project description:Kees2018 - Genome-scale constraint-based model of the mucin-degrader Akkermansia muciniphila This model is described in the article: Model-driven design of a minimal medium for Akkermansia muciniphila confirms mucus adaptation. van der Ark KCH, Aalvink S, Suarez-Diez M, Schaap PJ, de Vos WM, Belzer C. Microb Biotechnol 2018 Jan; : Abstract: The abundance of the human intestinal symbiont Akkermansia muciniphila has found to be inversely correlated with several diseases, including metabolic syndrome and obesity. A. muciniphila is known to use mucin as sole carbon and nitrogen source. To study the physiology and the potential for therapeutic applications of this bacterium, we designed a defined minimal medium. The composition of the medium was based on the genome-scale metabolic model of A. muciniphila and the composition of mucin. Our results indicate that A. muciniphila does not code for GlmS, the enzyme that mediates the conversion of fructose-6-phosphate (Fru6P) to glucosamine-6-phosphate (GlcN6P), which is essential in peptidoglycan formation. The only annotated enzyme that could mediate this conversion is Amuc-NagB on locus Amuc_1822. We found that Amuc-NagB was unable to form GlcN6P from Fru6P at physiological conditions, while it efficiently catalyzed the reverse reaction. To overcome this inability, N-acetylglucosamine needs to be present in the medium for A. muciniphila growth. With these findings, the genome-scale metabolic model was updated and used to accurately predict growth of A. muciniphila on synthetic media. The finding that A. muciniphila has a necessity for GlcNAc, which is present in mucin further prompts the adaptation to its mucosal niche. This model is hosted on BioModels Database and identified by: MODEL1710040000. To cite BioModels Database, please use: Chelliah V et al. BioModels: ten-year anniversary. Nucl. Acids Res. 2015, 43(Database issue):D542-8. To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.

Project description:The large-scale application of genomic and metagenomic sequencing technologies has yielded a number of insights about the metabolic potential of symbiotic human gut microbes. Bacteria that colonize the mucosal layer that overlies the gut epithelium have access to highly-sulfated polysaccharides (i.e., mucin oligosaccharides and glycosaminoglycans), which they could potentially forage as nutrient sources. To be active, sulfatases must undergo a critical post-translational modification catalyzed in anaerobic bacteria by the AdoMet enzyme anSME (anaerobic Sulfatase-Maturating Enzyme). In the present study, we have tested the role of this pathway in the prominent gut symbiont Bacteroides thetaiotaomicron, which possesses more predicted sulfatases (28) than in the human genome and a single predicted anSME. In vitro studies revealed that deletion of its anSME (BT0238) results in loss of sulfatase activity and impaired ability to use sulfated polysaccharides as carbon sources. Co-colonization of germ-free animals with both isogenic strains, or invasion experiments involving the introduction of one then the other strain, established that anSME activity and the sulfatases that are activated via this pathway, are important fitness factors for B. thetaiotaomicron, especially when mice are fed a simple sugar diet that requires this saccharolytic bacterium to adaptively forage on host glycans as nutrients. Whole genome transcriptional profiling of wild-type and the anSME mutant in vivo revealed that loss of this enzyme alters expression of genes involved in mucin utilization and that this disrupted ability to access mucosal glycans likely underlies the observed dramatic colonization defect. Comparative genomic analysis reveals that 100% of 46 fully sequenced human gut Bacteroidetes contain homologs of BT0238 and genes encoding sulfatases, suggesting that this is an important and evolutionarily conserved feature. Three replicate samples from 4 different biological treatment groups: 1. Wild-type B. thetaiotaomicron from the cecum of gnotobiotic mice fed a simple-sugar diet; 2. chuR mutant B. thetaiotaomicron from the cecum of gnotobiotic mice fed a simple-sugar diet; 3. Wild-type B. thetaiotaomicron from the cecum of gnotobiotic mice fed a plant-rich diet; 4. chuR mutant B. thetaiotaomicron from the cecum of gnotobiotic mice fed a plant-rich diet.

Dataset Information

Mucosal Glycan Foraging Enhances the Fitness and Transmission of a Saccharolytic Human Distal Gut Symbiont

Publications

Mucosal glycan foraging enhances fitness and transmission of a saccharolytic human gut bacterial symbiont.

Similar Datasets

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