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PMID: 24330590 Published · epublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

Polysaccharides utilization in human gut bacterium Bacteroides thetaiotaomicron: comparative genomics reconstruction of metabolic and regulatory networks.

BMC genomics ·Vol. 14 ·2013-12-12 ·Pages 873

Ravcheev DA, Godzik A, Osterman AL, Rodionov DA

Abstract

Bacteroides thetaiotaomicron, a predominant member of the human gut microbiota, is characterized by its ability to utilize a wide variety of polysaccharides using the extensive saccharolytic machinery that is controlled by an expanded repertoire of transcription factors (TFs). The availability of genomic sequences for multiple Bacteroides species opens an opportunity for their comparative analysis to enable characterization of their metabolic and regulatory networks. A comparative genomics approach was applied for the reconstruction and functional annotation of the carbohydrate utilization regulatory networks in 11 Bacteroides genomes. Bioinformatics analysis of promoter regions revealed putative DNA-binding motifs and regulons for 31 orthologous TFs in the Bacteroides. Among the analyzed TFs there are 4 SusR-like regulators, 16 AraC-like hybrid two-component systems (HTCSs), and 11 regulators from other families. Novel DNA motifs of HTCSs and SusR-like regulators in the Bacteroides have the common structure of direct repeats with a long spacer between two conserved sites. The inferred regulatory network in B. thetaiotaomicron contains 308 genes encoding polysaccharide and sugar catabolic enzymes, carbohydrate-binding and transport systems, and TFs. The analyzed TFs control pathways for utilization of host and dietary glycans to monosaccharides and their further interconversions to intermediates of the central metabolism. The reconstructed regulatory network allowed us to suggest and refine specific functional assignments for sugar catabolic enzymes and transporters, providing a substantial improvement to the existing metabolic models for B. thetaiotaomicron. The obtained collection of reconstructed TF regulons is available in the RegPrecise database (http://regprecise.lbl.gov).

MeSH Terms
Bacterial Proteins/genetics,metabolism Bacteroides/classification,genetics,metabolism Base Sequence Binding Sites Gastrointestinal Tract/microbiology Gene Expression Regulation, Bacterial Gene Regulatory Networks Genomics Humans Metabolic Networks and Pathways Nucleotide Motifs Phylogeny Polysaccharides/metabolism Position-Specific Scoring Matrices Trans-Activators/genetics,metabolism Transcription Factors/genetics,metabolism
Chemicals
Bacterial Proteins Polysaccharides SusR protein, Bacteroides thetaiotaomicron Trans-Activators Transcription Factors
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Ravcheev Dmitry A
Godzik Adam
Osterman Andrei L
Rodionov Dmitry A
Sanford-Burnham Medical Research Institute, La Jolla, California 92037, USA. rodionov@burnham.org.
References (66)
66 references, click to expand
  1. Genomic reconstruction of transcriptional regulatory networks in lactic acid bacteria.
    BMC Genomics. 2013 Feb 12;14:94 PMID: 23398941
  2. RegPredict: an integrated system for regulon inference in prokaryotes by comparative genomics approach.
    Nucleic Acids Res. 2010 Jul;38(Web Server issue):W299-307 PMID: 20542910
  3. Evolutionary bases of carbohydrate recognition and substrate discrimination in the ROK protein family.
    J Mol Evol. 2010 Jun;70(6):545-56 PMID: 20512568
  4. Dynamic responses of Bacteroides thetaiotaomicron during growth on glycan mixtures.
    Mol Microbiol. 2013 Jun;88(5):876-90 PMID: 23646867
  5. The Carbohydrate-Active EnZymes database (CAZy): an expert resource for Glycogenomics.
    Nucleic Acids Res. 2009 Jan;37(Database issue):D233-8 PMID: 18838391
  6. [Software for analyzing bacterial genomes].
    Mol Biol (Mosk). 2000 Mar-Apr;34(2):253-62 PMID: 10779952
  7. Automated genome annotation and metabolic model reconstruction in the SEED and Model SEED.
    Methods Mol Biol. 2013;985:17-45 PMID: 23417797
  8. The subsystems approach to genome annotation and its use in the project to annotate 1000 genomes.
    Nucleic Acids Res. 2005 Oct 07;33(17):5691-702 PMID: 16214803
  9. RegPrecise 3.0--a resource for genome-scale exploration of transcriptional regulation in bacteria.
    BMC Genomics. 2013 Nov 01;14:745 PMID: 24175918
  10. Message from a human gut symbiont: sensitivity is a prerequisite for sharing.
    Trends Microbiol. 2004 Jan;12(1):21-8 PMID: 14700548
  11. Systems-level characterization of a host-microbe metabolic symbiosis in the mammalian gut.
    Gut Microbes. 2013 Jan-Feb;4(1):28-40 PMID: 23022739
  12. Transcriptional regulation of NAD metabolism in bacteria: NrtR family of Nudix-related regulators.
    Nucleic Acids Res. 2008 Apr;36(6):2047-59 PMID: 18276643
  13. Rhamnose catabolism in Bacteroides thetaiotaomicron is controlled by the positive transcriptional regulator RhaR.
    Res Microbiol. 2008 Nov-Dec;159(9-10):678-84 PMID: 18848625
  14. How glycan metabolism shapes the human gut microbiota.
    Nat Rev Microbiol. 2012 Apr 11;10(5):323-35 PMID: 22491358
  15. Comparative genomic reconstruction of transcriptional regulatory networks in bacteria.
    Chem Rev. 2007 Aug;107(8):3467-97 PMID: 17636889
  16. Comparative genomic reconstruction of transcriptional networks controlling central metabolism in the Shewanella genus.
    BMC Genomics. 2011 Jun 15;12 Suppl 1:S3 PMID: 21810205
  17. Studies of the distribution of Escherichia coli cAMP-receptor protein and RNA polymerase along the E. coli chromosome.
    Proc Natl Acad Sci U S A. 2005 Dec 6;102(49):17693-8 PMID: 16301522
  18. Comparative genomics of regulation of fatty acid and branched-chain amino acid utilization in proteobacteria.
    J Bacteriol. 2009 Jan;191(1):52-64 PMID: 18820024
  19. Accessing the SEED genome databases via Web services API: tools for programmers.
    BMC Bioinformatics. 2010 Jun 14;11:319 PMID: 20546611
  20. From genomics to chemical genomics: new developments in KEGG.
    Nucleic Acids Res. 2006 Jan 1;34(Database issue):D354-7 PMID: 16381885
  21. A genomic view of the human-Bacteroides thetaiotaomicron symbiosis.
    Science. 2003 Mar 28;299(5615):2074-6 PMID: 12663928
  22. Pectin: cell biology and prospects for functional analysis.
    Plant Mol Biol. 2001 Sep;47(1-2):9-27 PMID: 11554482
  23. Chapter 1: Variation in form and function the helix-turn-helix regulators of the GntR superfamily.
    Adv Appl Microbiol. 2009;69:1-22 PMID: 19729089
  24. Inference of the transcriptional regulatory network in Staphylococcus aureus by integration of experimental and genomics-based evidence.
    J Bacteriol. 2011 Jul;193(13):3228-40 PMID: 21531804
  25. How host-microbial interactions shape the nutrient environment of the mammalian intestine.
    Annu Rev Nutr. 2002;22:283-307 PMID: 12055347
  26. Inferring phylogenies from protein sequences by parsimony, distance, and likelihood methods.
    Methods Enzymol. 1996;266:418-27 PMID: 8743697
  27. Glycan recognition by the Bacteroidetes Sus-like systems.
    Curr Opin Struct Biol. 2012 Oct;22(5):563-9 PMID: 22819666
  28. Evolution of symbiotic bacteria in the distal human intestine.
    PLoS Biol. 2007 Jul;5(7):e156 PMID: 17579514
  29. Overexpression of the rhamnose catabolism regulatory protein, RhaR: a novel mechanism for metronidazole resistance in Bacteroides thetaiotaomicron.
    J Antimicrob Chemother. 2009 Aug;64(2):267-73 PMID: 19525515
  30. Dendroscope: An interactive viewer for large phylogenetic trees.
    BMC Bioinformatics. 2007 Nov 22;8:460 PMID: 18034891
  31. Gut microbiome-host interactions in health and disease.
    Genome Med. 2011 Mar 04;3(3):14 PMID: 21392406
  32. MetaLocGramN: A meta-predictor of protein subcellular localization for Gram-negative bacteria.
    Biochim Biophys Acta. 2012 Dec;1824(12):1425-33 PMID: 22705560
  33. Glycans and neural cell interactions.
    Nat Rev Neurosci. 2004 Mar;5(3):195-208 PMID: 14976519
  34. Regulation of the expression of genes involved in NAD de novo biosynthesis in Corynebacterium glutamicum.
    Appl Environ Microbiol. 2010 Aug;76(16):5488-95 PMID: 20601509
  35. Transcriptional regulation of NAD metabolism in bacteria: genomic reconstruction of NiaR (YrxA) regulon.
    Nucleic Acids Res. 2008 Apr;36(6):2032-46 PMID: 18276644
  36. Structural biology of pectin degradation by Enterobacteriaceae.
    Microbiol Mol Biol Rev. 2008 Jun;72(2):301-16, table of contents PMID: 18535148
  37. Control of proteobacterial central carbon metabolism by the HexR transcriptional regulator: a case study in Shewanella oneidensis.
    J Biol Chem. 2011 Oct 14;286(41):35782-35794 PMID: 21849503
  38. Transcriptional regulation of central carbon and energy metabolism in bacteria by redox-responsive repressor Rex.
    J Bacteriol. 2012 Mar;194(5):1145-57 PMID: 22210771
  39. Control of bacterial virulence by AraC-like regulators that respond to chemical signals.
    Trends Microbiol. 2011 Mar;19(3):128-35 PMID: 21215638
  40. Comparative metagenomics revealed commonly enriched gene sets in human gut microbiomes.
    DNA Res. 2007 Aug 31;14(4):169-81 PMID: 17916580
  41. WebLogo: a sequence logo generator.
    Genome Res. 2004 Jun;14(6):1188-90 PMID: 15173120
  42. Genomic reconstruction of the transcriptional regulatory network in Bacillus subtilis.
    J Bacteriol. 2013 Jun;195(11):2463-73 PMID: 23504016
  43. Phylogenetic footprinting of hypersensitive site 3 of the beta-globin locus control region.
    Blood. 1997 May 1;89(9):3457-69 PMID: 9129054
  44. UniProt Knowledgebase: a hub of integrated protein data.
    Database (Oxford). 2011 Mar 29;2011:bar009 PMID: 21447597
  45. Mucosal glycan foraging enhances fitness and transmission of a saccharolytic human gut bacterial symbiont.
    Cell Host Microbe. 2008 Nov 13;4(5):447-57 PMID: 18996345
  46. Allostery in the LacI/GalR family: variations on a theme.
    Curr Opin Microbiol. 2009 Apr;12(2):129-37 PMID: 19269243
  47. Enterotypes of the human gut microbiome.
    Nature. 2011 May 12;473(7346):174-80 PMID: 21508958
  48. Complex glycan catabolism by the human gut microbiota: the Bacteroidetes Sus-like paradigm.
    J Biol Chem. 2009 Sep 11;284(37):24673-7 PMID: 19553672
  49. MicrobesOnline: an integrated portal for comparative and functional genomics.
    Nucleic Acids Res. 2010 Jan;38(Database issue):D396-400 PMID: 19906701
  50. KEGG: kyoto encyclopedia of genes and genomes.
    Nucleic Acids Res. 2000 Jan 1;28(1):27-30 PMID: 10592173
  51. Eating for two: how metabolism establishes interspecies interactions in the gut.
    Cell Host Microbe. 2011 Oct 20;10(4):336-47 PMID: 22018234
  52. A molecular sensor that allows a gut commensal to control its nutrient foundation in a competitive ecosystem.
    Proc Natl Acad Sci U S A. 1999 Aug 17;96(17):9833-8 PMID: 10449780
  53. Transcriptional regulation of the carbohydrate utilization network in Thermotoga maritima.
    Front Microbiol. 2013 Aug 23;4:244 PMID: 23986752
  54. Specificity of polysaccharide use in intestinal bacteroides species determines diet-induced microbiota alterations.
    Cell. 2010 Jun 25;141(7):1241-52 PMID: 20603004
  55. Phylogenetic footprinting of transcription factor binding sites in proteobacterial genomes.
    Nucleic Acids Res. 2001 Feb 1;29(3):774-82 PMID: 11160901
  56. The gut microbiota shapes intestinal immune responses during health and disease.
    Nat Rev Immunol. 2009 May;9(5):313-23 PMID: 19343057
  57. Effect of regulatory protein levels on utilization of starch by Bacteroides thetaiotaomicron.
    J Bacteriol. 1996 Dec;178(24):7180-6 PMID: 8955400
  58. Functional diversification of ROK-family transcriptional regulators of sugar catabolism in the Thermotogae phylum.
    Nucleic Acids Res. 2013 Jan;41(2):790-803 PMID: 23209028
  59. A hybrid two-component system protein of a prominent human gut symbiont couples glycan sensing in vivo to carbohydrate metabolism.
    Proc Natl Acad Sci U S A. 2006 Jun 6;103(23):8834-9 PMID: 16735464
  60. Quantifying similarity between motifs.
    Genome Biol. 2007;8(2):R24 PMID: 17324271
  61. MUSCLE: multiple sequence alignment with high accuracy and high throughput.
    Nucleic Acids Res. 2004 Mar 19;32(5):1792-7 PMID: 15034147
  62. Transcriptional regulation of transport and utilization systems for hexuronides, hexuronates and hexonates in gamma purple bacteria.
    Mol Microbiol. 2000 Nov;38(4):673-83 PMID: 11115104
  63. Recognition and degradation of plant cell wall polysaccharides by two human gut symbionts.
    PLoS Biol. 2011 Dec;9(12):e1001221 PMID: 22205877
  64. Diversity of the human intestinal microbial flora.
    Science. 2005 Jun 10;308(5728):1635-8 PMID: 15831718
  65. Coordinate regulation of glycan degradation and polysaccharide capsule biosynthesis by a prominent human gut symbiont.
    J Biol Chem. 2009 Jul 3;284(27):18445-57 PMID: 19403529
  66. A scissor blade-like closing mechanism implicated in transmembrane signaling in a Bacteroides hybrid two-component system.
    Proc Natl Acad Sci U S A. 2012 May 8;109(19):7298-303 PMID: 22532667
Article Info
Journal
BMC genomics
Abbr.
BMC Genomics
ISSN
1471-2164
DOI
10.1186/1471-2164-14-873
Email
rodionov@burnham.org
Published
2013-12-12
Epub
2013-00-12
Pages
873
Language
English
Region
England
NLM ID
100965258
PMCID
PMC3878776
Subset
IM
Grants
NIGMS NIH HHS · U54 GM094586-04 · United States
External Links
PubMed source DOI: 10.1186/1471-2164-14-873 PMC Full Text View journal details
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