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PMID: 17617894 Published · ppublish English Journal Article

Modeling Neisseria meningitidis metabolism: from genome to metabolic fluxes.

Genome biology ·Vol. 8 ·No. 7 ·2007-00-00 ·Pages R136

Baart GJ, Zomer B, de Haan A, van der Pol LA, Beuvery EC, Tramper J, Martens DE

Abstract

Neisseria meningitidis is a human pathogen that can infect diverse sites within the human host. The major diseases caused by N. meningitidis are responsible for death and disability, especially in young infants. In general, most of the recent work on N. meningitidis focuses on potential antigens and their functions, immunogenicity, and pathogenicity mechanisms. Very little work has been carried out on Neisseria primary metabolism over the past 25 years. Using the genomic database of N. meningitidis serogroup B together with biochemical and physiological information in the literature we constructed a genome-scale flux model for the primary metabolism of N. meningitidis. The validity of a simplified metabolic network derived from the genome-scale metabolic network was checked using flux-balance analysis in chemostat cultures. Several useful predictions were obtained from in silico experiments, including substrate preference. A minimal medium for growth of N. meningitidis was designed and tested successfully in batch and chemostat cultures. The verified metabolic model describes the primary metabolism of N. meningitidis in a chemostat in steady state. The genome-scale model is valuable because it offers a framework to study N. meningitidis metabolism as a whole, or certain aspects of it, and it can also be used for the purpose of vaccine process development (for example, the design of growth media). The flux distribution of the main metabolic pathways (that is, the pentose phosphate pathway and the Entner-Douderoff pathway) indicates that the major part of pyruvate (69%) is synthesized through the ED-cleavage, a finding that is in good agreement with literature.

MeSH Terms
Computational Biology Genome, Bacterial Metabolic Networks and Pathways/genetics Models, Biological Neisseria meningitidis/genetics,metabolism
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Baart Gino J E
Unit Research & Development, Netherlands Vaccine Institute (NVI), PO Box 457, 3720 AL Bilthoven, The Netherlands. [email protected]
Zomer Bert
de Haan Alex
van der Pol Leo A
Beuvery E Coen
Tramper Johannes
Martens Dirk E
References (115)
115 references, click to expand
  1. Integrating high-throughput and computational data elucidates bacterial networks.
    Nature. 2004 May 6;429(6987):92-6 PMID: 15129285
  2. Viability of a capsule- and lipopolysaccharide-deficient mutant of Neisseria meningitidis.
    Infect Immun. 2005 Sep;73(9):6194-7 PMID: 16113348
  3. Genome annotation errors in pathway databases due to semantic ambiguity in partial EC numbers.
    Nucleic Acids Res. 2005;33(13):4035-9 PMID: 16034025
  4. Nod2 is a general sensor of peptidoglycan through muramyl dipeptide (MDP) detection.
    J Biol Chem. 2003 Mar 14;278(11):8869-72 PMID: 12527755
  5. Identification of an outer membrane protein required for the transport of lipopolysaccharide to the bacterial cell surface.
    Proc Natl Acad Sci U S A. 2004 Jun 22;101(25):9417-22 PMID: 15192148
  6. The pathogen Neisseria meningitidis requires oxygen, but supplements growth by denitrification. Nitrite, nitric oxide and oxygen control respiratory flux at genetic and metabolic levels.
    Mol Microbiol. 2005 Nov;58(3):800-9 PMID: 16238628
  7. Monte Carlo sampling and principal component analysis of flux distributions yield topological and modular information on metabolic networks.
    J Theor Biol. 2006 Sep 21;242(2):389-400 PMID: 16860341
  8. Nutritional profiles of Neisseria gonorrhoeae, Neisseria meningitidis, and Neisseria lactamica in chemically defined media and the use of growth requirements for gonococcal typing.
    J Infect Dis. 1973 Aug;128(2):178-94 PMID: 4198720
  9. Regulation of the ldhA gene, encoding the fermentative lactate dehydrogenase of Escherichia coli.
    Microbiology. 2001 Sep;147(Pt 9):2437-46 PMID: 11535784
  10. Fast atom bombardment mass spectrometry and tandem mass spectrometry of biologically active peptidoglycan monomers from Neisseria gonorrhoeae.
    J Biol Chem. 1987 Jun 5;262(16):7514-22 PMID: 3108252
  11. Sialic acids as ligands in recognition phenomena.
    FASEB J. 1997 Mar;11(4):248-55 PMID: 9068613
  12. In silico predictions of Escherichia coli metabolic capabilities are consistent with experimental data.
    Nat Biotechnol. 2001 Feb;19(2):125-30 PMID: 11175725
  13. Glutamate dehydrogenases in Neisseria meningitidis.
    Acta Pathol Microbiol Scand B Microbiol Immunol. 1973 Feb;81(1):43-8 PMID: 4147033
  14. Genome-scale microbial in silico models: the constraints-based approach.
    Trends Biotechnol. 2003 Apr;21(4):162-9 PMID: 12679064
  15. Functional ingredient production: application of global metabolic models.
    Curr Opin Biotechnol. 2005 Apr;16(2):190-7 PMID: 15831386
  16. Regulated covalent modifications of lipid A.
    J Endotoxin Res. 2001;7(1):73-8 PMID: 11521087
  17. Oxidation of amino acids and compounds associated with the tricarboxylic acid cycle by Neisseria gonorrhoeae.
    J Bacteriol. 1953 Apr;65(4):368-77 PMID: 13069389
  18. An NMR and enzyme study of the carbon metabolism of Neisseria meningitidis.
    Microbiology. 2001 Jun;147(Pt 6):1473-82 PMID: 11390678
  19. Variability of peptidoglycan structural parameters in gram-negative bacteria.
    FEMS Microbiol Lett. 1995 Jan 1;125(1):95-100 PMID: 7867925
  20. Glucose catabolism in Neisseria meningitidis. 1. Glucose oxidation and intermediate reactions of the Embden-Meyerhof pathway.
    Acta Pathol Microbiol Scand. 1961;53:71-83 PMID: 14452925
  21. Host recognition of bacterial muramyl dipeptide mediated through NOD2. Implications for Crohn's disease.
    J Biol Chem. 2003 Feb 21;278(8):5509-12 PMID: 12514169
  22. Detailed structural analysis of the peptidoglycan of the human pathogen Neisseria meningitidis.
    J Biol Chem. 2003 Aug 22;278(34):31521-8 PMID: 12799361
  23. Radiorespirometric studies in genus Neisserai. I. The catabolism of glucose.
    Acta Pathol Microbiol Scand B. 1975 Aug;83(4):353-66 PMID: 1155121
  24. Biosynthesis of sialic acids by Neisseria meningitidis.
    J Biol Chem. 1962 Nov;237:3520-6 PMID: 13971393
  25. Defenses against oxidative stress in Neisseria gonorrhoeae and Neisseria meningitidis: distinctive systems for different lifestyles.
    J Infect Dis. 2004 Jul 1;190(1):136-47 PMID: 15195253
  26. Microbial metabolomics: replacing trial-and-error by the unbiased selection and ranking of targets.
    J Ind Microbiol Biotechnol. 2005 Jun;32(6):234-52 PMID: 15895265
  27. Vaccine prevention of meningococcal disease, coming soon?
    Vaccine. 2001 Dec 12;20(5-6):666-87 PMID: 11738731
  28. Serum bactericidal activity and isotype distribution of antibodies in toddlers and schoolchildren after vaccination with RIVM hexavalent PorA vesicle vaccine.
    Vaccine. 2001 Nov 12;20(3-4):352-8 PMID: 11672897
  29. Glucokinase and glucose 6-phosphate dehydrogenase in Neisseria.
    Acta Pathol Microbiol Scand B Microbiol Immunol. 1974 Apr;82(2):201-6 PMID: 4212034
  30. Vaccines for prevention of meningococcal disease.
    Clin Microbiol Rev. 1989 Apr;2 Suppl:S134-8 PMID: 2497956
  31. Radiorespirometric studies in genus Neisseria. 2. The catabolism of glutamate and fumarate.
    Acta Pathol Microbiol Scand B. 1976 Feb;84(1):1-8 PMID: 814781
  32. Sialylation of Neisseria meningitidis lipooligosaccharide inhibits serum bactericidal activity by masking lacto-N-neotetraose.
    Infect Immun. 1997 Nov;65(11):4436-44 PMID: 9353017
  33. Effect of Escherichia coli biomass composition on central metabolic fluxes predicted by a stoichiometric model.
    Biotechnol Bioeng. 1998 Oct 20;60(2):230-8 PMID: 10099424
  34. Application of macroscopic balances to the identification of gross measurement errors.
    Biotechnol Bioeng. 1983 Sep;25(9):2177-208 PMID: 18574815
  35. D-lactic acid metabolism after an oral load of DL-lactate.
    Clin Nutr. 1990 Feb;9(1):23-8 PMID: 16837316
  36. In silico reconstruction of the metabolic pathways of Lactobacillus plantarum: comparing predictions of nutrient requirements with those from growth experiments.
    Appl Environ Microbiol. 2005 Nov;71(11):7253-62 PMID: 16269766
  37. Cloning of a Neisseria meningitidis gene for L-lactate dehydrogenase (L-LDH): evidence for a second meningococcal L-LDH with different regulation.
    J Bacteriol. 1996 Aug;178(16):4807-13 PMID: 8759842
  38. Uncovering transcriptional regulation of metabolism by using metabolic network topology.
    Proc Natl Acad Sci U S A. 2005 Feb 22;102(8):2685-9 PMID: 15710883
  39. Analysis of Neisseria gonorrhoeae peptidoglycan by reverse-phase, high-pressure liquid chromatography.
    J Bacteriol. 1985 Jul;163(1):69-74 PMID: 3924898
  40. Effect of glutamate on exogenous citrate catabolism of Neisseria meningitidis and of other species of Neisseria.
    J Bacteriol. 1971 Jun;106(3):819-23 PMID: 4997540
  41. A functional genomics approach using metabolomics and in silico pathway analysis.
    Biotechnol Bioeng. 2002 Sep 30;79(7):703-12 PMID: 12209793
  42. Activities of some enzymes concerning pyruvate metabolism in Neisseria.
    Acta Pathol Microbiol Scand B Microbiol Immunol. 1974 Dec;82(6):843-8 PMID: 4218441
  43. Endogenous incorporation of 32 P in Neisseria meningitidis. I. The effects of CO2 and electron flux.
    Acta Pathol Microbiol Scand B Microbiol Immunol. 1970;78(3):337-42 PMID: 4320022
  44. Function of neisserial outer membrane phospholipase a in autolysis and assessment of its vaccine potential.
    Infect Immun. 2005 Apr;73(4):2222-31 PMID: 15784566
  45. The genetic basis of the phase variation repertoire of lipopolysaccharide immunotypes in Neisseria meningitidis.
    Microbiology. 1999 Nov;145 ( Pt 11):3013-21 PMID: 10589709
  46. Cytochrome c, an ideal antioxidant.
    Biochem Soc Trans. 2003 Dec;31(Pt 6):1312-5 PMID: 14641051
  47. Physiology and metabolism of Neisseria gonorrhoeae and Neisseria meningitidis: implications for pathogenesis.
    Clin Microbiol Rev. 1989 Apr;2 Suppl:S35-40 PMID: 2497961
  48. Microbial identification by gas chromatography.
    J R Nav Med Serv. 1988 Winter;74(3):141-6 PMID: 3076902
  49. Stoichiometric analysis of animal cell growth and its application in medium design.
    Biotechnol Bioeng. 1994 May;43(11):1164-74 PMID: 18615530
  50. Metabolism of pyrimidine bases and nucleosides in Neisseria meningitidis.
    J Bacteriol. 1979 May;138(2):320-3 PMID: 108255
  51. Microdermatology: cell surface in the interaction of microbes with the external world.
    J Bacteriol. 1999 Jan;181(1):4-8 PMID: 9864305
  52. An analysis of the binding of repressor protein ModE to modABCD (molybdate transport) operator/promoter DNA of Escherichia coli.
    J Biol Chem. 1999 Aug 20;274(34):24308-15 PMID: 10446207
  53. Gas chromatography of bacterial whole cell methanolysates; V. Fatty acid composition of Neisseriae and Moraxellae.
    Acta Pathol Microbiol Scand B Microbiol Immunol. 1974 Dec;82(6):767-79 PMID: 4218439
  54. Oxidation of D-lactate and L-lactate by Neisseria meningitidis: purification and cloning of meningococcal D-lactate dehydrogenase.
    J Bacteriol. 1993 Oct;175(20):6382-91 PMID: 8407815
  55. Composition of the peptidoglycan of Haemophilus influenzae.
    J Biol Chem. 1993 Jun 5;268(16):11594-8 PMID: 8505290
  56. Phospholipid composition and phospholipase A activity of Neisseria gonorrhoeae.
    J Bacteriol. 1976 Aug;127(2):874-80 PMID: 821921
  57. Roles of thiol-redox pathways in bacteria.
    Annu Rev Microbiol. 2001;55:21-48 PMID: 11544348
  58. O-acetylated peptidoglycan: its occurrence, pathobiological significance, and biosynthesis.
    Can J Microbiol. 1992 Feb;38(2):85-91 PMID: 1521192
  59. An IgG monoclonal antibody to group B meningococci cross-reacts with developmentally regulated polysialic acid units of glycoproteins in neural and extraneural tissues.
    J Immunol. 1987 Jun 15;138(12):4402-7 PMID: 3108388
  60. Reverse vaccinology, a genome-based approach to vaccine development.
    Vaccine. 2001 Mar 21;19(17-19):2688-91 PMID: 11257410
  61. Linear constraint relations in biochemical reaction systems: I. Classification of the calculability and the balanceability of conversion rates.
    Biotechnol Bioeng. 1994 Jan 5;43(1):3-10 PMID: 18613305
  62. Microaerobic denitrification in Neisseria meningitidis.
    Biochem Soc Trans. 2005 Feb;33(Pt 1):134-6 PMID: 15667285
  63. A review of vaccine research and development: meningococcal disease.
    Vaccine. 2006 May 29;24(22):4692-700 PMID: 16621189
  64. Terminal branching of the respiratory electron transport chain in Neisseria meningitidis.
    J Bacteriol. 1980 Jun;142(3):879-87 PMID: 6769915
  65. Metabolic flux analysis of Escherichia coli in glucose-limited continuous culture. I. Growth-rate-dependent metabolic efficiency at steady state.
    Microbiology. 2005 Mar;151(Pt 3):693-706 PMID: 15758216
  66. Intermediate reactions of the tricarboxylic acid cycle in meningococci.
    Acta Pathol Microbiol Scand. 1960;48:121-32 PMID: 14408280
  67. Unusual composition of peptidoglycan in Bordetella pertussis.
    J Biol Chem. 1989 Jul 5;264(19):11093-8 PMID: 2544584
  68. Identification of vaccine candidates against serogroup B meningococcus by whole-genome sequencing.
    Science. 2000 Mar 10;287(5459):1816-20 PMID: 10710308
  69. In silico genome-scale reconstruction and validation of the Staphylococcus aureus metabolic network.
    Biotechnol Bioeng. 2005 Dec 30;92(7):850-64 PMID: 16155945
  70. L-cysteine oxidase activity in the membrane of Neisseria meningitidis.
    J Bacteriol. 1981 Jan;145(1):280-7 PMID: 6780513
  71. Pyrimidine biosynthesis in Neisseria meningitidis. 1. Demonstration of enzyme activities.
    Acta Pathol Microbiol Immunol Scand B. 1983 Aug;91(4):251-5 PMID: 6137930
  72. Sulphur acquisition by Neisseria meningitidis.
    Can J Microbiol. 1984 Dec;30(12):1453-7 PMID: 6441640
  73. Applications of cellular fatty acid analysis.
    Clin Microbiol Rev. 1991 Oct;4(4):422-38 PMID: 1747860
  74. Periplasmic superoxide dismutase in meningococcal pathogenicity.
    Infect Immun. 1998 Jan;66(1):213-7 PMID: 9423860
  75. The composition of the murein of Escherichia coli.
    J Biol Chem. 1988 Jul 25;263(21):10088-95 PMID: 3292521
  76. Growth Requirements of the Meningococcus.
    J Bacteriol. 1942 Jun;43(6):757-61 PMID: 16560537
  77. Update on meningococcal disease with emphasis on pathogenesis and clinical management.
    Clin Microbiol Rev. 2000 Jan;13(1):144-66, table of contents PMID: 10627495
  78. Variation in lipid A structure in the pathogenic yersiniae.
    Mol Microbiol. 2004 Jun;52(5):1363-73 PMID: 15165239
  79. Conjugates and reverse vaccinology to eliminate bacterial meningitis.
    Vaccine. 2001 Mar 21;19(17-19):2319-22 PMID: 11257355
  80. A PhoP/PhoQ-induced Lipase (PagL) that catalyzes 3-O-deacylation of lipid A precursors in membranes of Salmonella typhimurium.
    J Biol Chem. 2001 Mar 23;276(12):9083-92 PMID: 11108722
  81. Structural characterization of the lipid A component of pathogenic Neisseria meningitidis.
    J Bacteriol. 1992 Mar;174(6):1793-800 PMID: 1548229
  82. Assimilation of nitrogen in meningococci grown with the ammonium ion as sole nitrogen source.
    Acta Pathol Microbiol Scand. 1959;46:320-32 PMID: 14408279
  83. Glucose metabolism in Neisseria gonorrhoeae.
    J Bacteriol. 1974 Nov;120(2):702-14 PMID: 4156358
  84. Physiology and metabolism of pathogenic neisseria: tricarboxylic acid cycle activity in Neisseria gonorrhoeae.
    J Bacteriol. 1976 Oct;128(1):192-201 PMID: 824268
  85. Integration of gene expression data into genome-scale metabolic models.
    Metab Eng. 2004 Oct;6(4):285-93 PMID: 15491858
  86. Construction of Neisseria meningitidis strains carrying multiple chromosomal copies of the porA gene for use in the production of a multivalent outer membrane vesicle vaccine.
    Vaccine. 1995 Mar;13(4):401-7 PMID: 7793138
  87. Lipid on capsular polysaccharides of gram-negative bacteria.
    J Biol Chem. 1981 Sep 10;256(17):8915-21 PMID: 7021555
  88. Observations on the metabolism of a strain of Neisseria catarrhalis.
    J Bacteriol. 1950 Feb;59(2):277-86 PMID: 15421956
  89. Development of vaccines against meningococcal disease.
    Lancet. 2002 Apr 27;359(9316):1499-508 PMID: 11988262
  90. Complete genome sequence of Neisseria meningitidis serogroup B strain MC58.
    Science. 2000 Mar 10;287(5459):1809-15 PMID: 10710307
  91. Alternative vaccine strategies to prevent serogroup B meningococcal diseases.
    Vaccine. 2001 Oct 15;20 Suppl 1:S24-6 PMID: 11587805
  92. 6-Phosphogluconate dehydrogenase and enzymes of the Entner-Doudoroff pathway in Neisseria.
    Acta Pathol Microbiol Scand B Microbiol Immunol. 1974 Apr;82(2):207-13 PMID: 4153167
  93. Phospholipids and fatty acids of Neisseria gonorrhoeae.
    J Bacteriol. 1975 Nov;124(2):713-7 PMID: 810478
  94. The bacterial cytochrome cbb3 oxidases.
    Biochim Biophys Acta. 2004 Apr 12;1655(1-3):388-99 PMID: 15100055
  95. In silico design and adaptive evolution of Escherichia coli for production of lactic acid.
    Biotechnol Bioeng. 2005 Sep 5;91(5):643-8 PMID: 15962337
  96. Cross-reactivity of antibodies against PorA after vaccination with a meningococcal B outer membrane vesicle vaccine.
    Infect Immun. 2003 Apr;71(4):1650-5 PMID: 12654777
  97. Growth Requirements and Metabolism of Neisseria intracellularis.
    J Bacteriol. 1945 Jul;50(1):109-15 PMID: 16560967
  98. Characterization and identification of vaccine candidate proteins through analysis of the group A Streptococcus surface proteome.
    Nat Biotechnol. 2006 Feb;24(2):191-7 PMID: 16415855
  99. Bacterial genomes pave the way to novel vaccines.
    Curr Opin Microbiol. 2004 Jun;7(3):314-20 PMID: 15196501
  100. Meningitis bacterium is viable without endotoxin.
    Nature. 1998 Apr 2;392(6675):449-50 PMID: 9548250
  101. Pyridine nucleotide independent oxidation of L-malate in genus Neisseria.
    Acta Pathol Microbiol Scand B. 1976 Feb;84(1):17-21 PMID: 814782
  102. Linear constraint relations in biochemical reaction systems: II. Diagnosis and estimation of gross errors.
    Biotechnol Bioeng. 1994 Jan 5;43(1):11-20 PMID: 18613306
  103. Metabolic analysis of adaptive evolution for in silico-designed lactate-producing strains.
    Biotechnol Bioeng. 2006 Dec 5;95(5):992-1002 PMID: 16807925
  104. Catabolic Activities of Neisseria meningitidis: Utilization of Succinate.
    J Bacteriol. 1970 Jan;101(1):133-7 PMID: 16559074
  105. Bacterial [Cu,Zn]-cofactored superoxide dismutase protects opsonized, encapsulated Neisseria meningitidis from phagocytosis by human monocytes/macrophages.
    Infect Immun. 2003 Mar;71(3):1604-7 PMID: 12595487
  106. Stoichiometric model of Escherichia coli metabolism: incorporation of growth-rate dependent biomass composition and mechanistic energy requirements.
    Biotechnol Bioeng. 1997 Nov 20;56(4):398-421 PMID: 18642243
  107. Cloning and molecular analysis of the galE gene of Neisseria meningitidis and its role in lipopolysaccharide biosynthesis.
    Mol Microbiol. 1993 Oct;10(2):361-9 PMID: 7934827
  108. The membrane phospholipids of Neisseria meningitidis and Neisseria gonorrhoeae as characterized by fast atom bombardment mass spectrometry.
    Microbiology. 2000 Aug;146 ( Pt 8):1901-11 PMID: 10931894
  109. Modification of lipid A biosynthesis in Neisseria meningitidis lpxL mutants: influence on lipopolysaccharide structure, toxicity, and adjuvant activity.
    Infect Immun. 2001 Oct;69(10):5981-90 PMID: 11553534
  110. The (alpha2-->8)-linked polysialic acid capsule and lipooligosaccharide structure both contribute to the ability of serogroup B Neisseria meningitidis to resist the bactericidal activity of normal human serum.
    Infect Immun. 1998 Dec;66(12):5939-47 PMID: 9826376
  111. Radiorespirometric studies in genus Neisseria. 3. The catabolism of pyruvate and acetate.
    Acta Pathol Microbiol Scand B. 1976 Feb;84(1):9-16 PMID: 814786
  112. Genealogy profiling through strain improvement by using metabolic network analysis: metabolic flux genealogy of several generations of lysine-producing corynebacteria.
    Appl Environ Microbiol. 2002 Dec;68(12):5843-59 PMID: 12450803
  113. Structure of the sialylated L3 lipopolysaccharide of Neisseria meningitidis.
    J Biol Chem. 1993 Jul 5;268(19):14146-52 PMID: 8314780
  114. Statistical reconciliation of the elemental and molecular biomass composition of Saccharomyces cerevisiae.
    Biotechnol Bioeng. 2001 Nov 5;75(3):334-44 PMID: 11590606
  115. Cell envelope alterations in antibiotic-sensitive and-resistant strains of Neisseria gonorrhoeae.
    J Bacteriol. 1978 Oct;136(1):391-401 PMID: 101519
Article Info
Journal
Genome biology
Abbr.
Genome Biol
ISSN
1474-760X
Published
2007-00-00
Pages
R136
Language
English
Region
England
NLM ID
100960660
PMCID
PMC2323225
Subset
IM
Analysis Services
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