, Volume 1, Issue 3, pp 235–242 | Cite as

Metabolomic diversity in the species Escherichia coli and its relationship to genetic population structure


The genomic richness and intra-species heterogeneity of the prokaryotic world is suggestive of extensive biochemical diversity. In this study, metabolomic profiling permitted a phylogenetic assessment of metabolic diversification amongst environmental, medical and laboratory strains of Escherichia coli. Strikingly, no two E. coli isolates exhibited the same metabolite pool profile. Only 27% of detected metabolite spots in 2-dimensional high-performance thin layer chromatography (2DHPTLC) were found in all strains, indicating that a relatively small core of metabolism is conserved across a species. The population structure determined using metabolomics exhibited clustering of strains in parallel to genetic relatedness, as established by multi-locus DNA sequencing. On the other hand, metabolome patterns did not cluster in parallel with the pathogenicity or environmental origins of strains, but some unique spots were found in most bacteria. These results suggest that great metabolic diversity, to the point of individuality, is likely to be characteristic of a bacterial species. Furthermore, the high resolving power of 2DHPTLC metabolite fingerprinting provides an economic and powerful means of using metabolomics for the analysis of evolutionary relationships and the precise typing of organisms.


two-dimensional high-performance thin layer chromatography 2DHPTLC bacterial metabolism Escherichia coli phylogenetics population structure 



We thank Peter Reeves for strains, Ruiting Lan for the MLST data, Kristin Miller for the first experiments on the ECOR strains as well as the ARC for funding support.


  1. Bergthorsson, U. and Ochman, H. (1998) Distribution of chromosome length variation in natural isolates of Escherichia coli. Mol. Biol. Evol. 15, 6–16.PubMedGoogle Scholar
  2. Blattner, F.R., Plunkett, G., Bloch, C.A., Perna, N.T., Burland, V., Riley, M., Colladovides, J., Glasner, J.D., Rode, C.K., Mayhew, G.F., Gregor, J., Davis, N.W., Kirkpatrick, H.A., Goeden, M.A., Rose, D.J., Mau, B. and Shao, Y. (1997) The complete genome sequence of Escherichia coli K-12. Science 277, 1453–1462.CrossRefPubMedGoogle Scholar
  3. Casabadan, M.J. (1976) Transposition and fusion of the lac genes to selected promoters in Escherichia coli using bacteriophage lambda and mu. J. Mol. Biol. 104, 541–555.CrossRefGoogle Scholar
  4. Covert, M.W., Knight, E.M., Reed, J.L., Herrgard, M.J. and Palsson, B.O. (2004) Integrating high-throughput and computational data elucidates bacterial networks. Nature 429, 92–96.CrossRefPubMedGoogle Scholar
  5. Feil, E.J. (2004) Small change: Keeping pace with microevolution. Nature Reviews Microbiology 2, 483–495.CrossRefPubMedGoogle Scholar
  6. Fiehn, O. (2001) Combining genomics, metabolome analysis and molecular modelling to understand metabolic networks. Comp. Funct. Genom. 2, 155–168.CrossRefGoogle Scholar
  7. Goodacre, R., Vaidyanathan, S., Dunn, W.B., Harrigan, G.G. and Kell, D.B. (2004) Metabolomics by numbers: Acquiring and understanding global metabolite data. Trends Biotechnol. 22, 245–252.CrossRefPubMedGoogle Scholar
  8. Hartl, D.L. and Dykhuizen, D.E. (1984) The population genetics of Escherichia coli. Annu. Rev. Genet. 18, 31–68.CrossRefPubMedGoogle Scholar
  9. Justice, S.S., Hung, C., Theriot, J.A., Fletcher, D.A., Anderson, G.G., Footer, M.J. and Hultgren, S.J. (2004) Differentiation and developmental pathways of uropathogenic Escherichia coli in urinary tract pathogenesis. Proc. Natl. Acad. Sci. U. S. A. 101, 1333–1338.CrossRefPubMedGoogle Scholar
  10. King, T., Ishihama, A., Kori, A. and Ferenci, T. (2004) A regulatory trade-off as a source of strain variation in the species Escherichia coli. J. Bacteriol. 186, 5614–5620.CrossRefPubMedGoogle Scholar
  11. Maharjan, R.P. and Ferenci, T. (2003) Global metabolite analysis: The influence of extraction methodology on metabolome profiles of Escherichia coli. Anal. Biochem. 313, 145–154.CrossRefPubMedGoogle Scholar
  12. Mahon, P. and Dupree, P. (2001) Quantitative and reproducible two-dimensional gel analysis using phoretix 2d full. Electrophoresis 22, 2075–2085.CrossRefPubMedGoogle Scholar
  13. Notley, L. and Ferenci, T. (1995) Differential expression of mal genes under cAMP and endogenous inducer control in nutrient stressed Escherichia coli. Mol. Microbiol. 16, 121–129.CrossRefPubMedGoogle Scholar
  14. Notley-McRobb, L., Seeto, S. and Ferenci, T. (2003) The influence of cellular physiology on the initiation of mutational pathways in Escherichia coli populations. Proc. R. Soc. Lond. Ser. B-Biol. Sci. 270, 843–848.CrossRefGoogle Scholar
  15. Ochman, H. and Selander, R.K. (1984) Standard reference strains of Escherichia coli from natural populations. J. Bacteriol. 157, 690–693.PubMedGoogle Scholar
  16. Peters, J.E., Thate, T.E. and Craig, N.L. (2003) Definition of the Escherichia coli MC4100 genome by use of a DNA array. J. Bacteriol. 185, 2017–2021.CrossRefPubMedGoogle Scholar
  17. Picard, B., Garcia, J.S., Gouriou, S., Duriez, P., Brahimi, N., Bingen, E., J., E. and Denamur, E. (1999) The link between phylogeny and virulence in Escherichia coli extraintestinal infection. Infect. Immun. 67, 546–553.PubMedGoogle Scholar
  18. Postgate, J. (1994) The outer reaches of life. Cambridge University Press, Cambridge.Google Scholar
  19. Pupo, G.M., Karaolis, D.K.R., Lan, R.T. and Reeves, P.R. (1997) Evolutionary relationships among pathogenic and nonpathogenic Escherichia coli strains inferred from multilocus enzyme electrophoresis and mdh sequence studies. Infect. Immun. 65, 2685–2692.PubMedGoogle Scholar
  20. Raamsdonk, L.M., Teusink, B., Broadhurst, D., Zhang, N.S., Hayes, A., Walsh, M.C., Berden, J.A., Brindle, K.M., Kell, D.B., Rowland, J.J., Westerhoff, H.V., van Dam, K. and Oliver, S.G. (2001) A functional genomics strategy that uses metabolome data to reveal the phenotype of silent mutations. Nat. Biotechnol. 19, 45–50.CrossRefPubMedGoogle Scholar
  21. Reid, S.D., Herbelin, C.J., Bumbaugh, A.C., Selander, R.K. and Whittam, T.S. (2000) Parallel evolution of virulence in pathogenic Escherichia coli. Nature 406, 64–67.CrossRefPubMedGoogle Scholar
  22. Rock, C.L., Lampe, J.W. and Patterson, R.E. (2000) Nutrition, genetics, and risks of cancer. Annu. Rev. Public Health 21, 47–64.CrossRefPubMedGoogle Scholar
  23. Sauer, U. (2004) High-throughput phenomics: Experimental methods for mapping fluxomes. Curr. Opin. Biotech. 15, 58–63.CrossRefPubMedGoogle Scholar
  24. Trulzsch, K., Hoffmann, H., Keller, C., Schubert, S., Bader, L., Heesemann, J. and Roggenkamp, A. (2003) Highly resistant metabolically deficient dwarf mutant of Escherichia coli is the cause of a chronic urinary tract infection. J. Clin. Microbiol. 41, 5689–5694.CrossRefPubMedGoogle Scholar
  25. Tweeddale, H., Notley-McRobb, L. and Ferenci, T. (1998) Effect of slow growth on metabolism of Escherichia coli, as revealed by global metabolite pool ("metabolome") analysis. J. Bacteriol. 180, 5109–5116.PubMedGoogle Scholar
  26. Vaidyanathan, S. (2005) Profiling microbial metabolomes: What do we stand to gain? Metabolomics 1, 17–28.CrossRefGoogle Scholar
  27. Venter, J.C., Remington, K., Heidelberg, J.F., Halpern, A.L., Rusch, D., Eisen, J.A., Wu, D.Y., Paulsen, I., Nelson, K.E., Nelson, W., Fouts, D.E., Levy, S., Knap, A.H., Lomas, M.W., Nealson, K., White, O., Peterson, J., Hoffman, J., Parsons, R., Baden-Tillson, H., Pfannkoch, C., Rogers, Y.H. and Smith, H.O. (2004) Environmental genome shotgun sequencing of the sargasso sea. Science 304, 66–74.CrossRefPubMedGoogle Scholar
  28. Welch, R.A., Burland, V., Plunkett, G., Redford, P., Roesch, P., Rasko, D., Buckles, E.L., Liou, S.R., Boutin, A., Hackett, J., Stroud, D., Mayhew, G.F., Rose, D.J., Zhou, S., Schwartz, D.C., Perna, N.T., Mobley, H.L.T., Donnenberg, M.S. and Blattner, F.R. (2002) Extensive mosaic structure revealed by the complete genome sequence of uropathogenic Escherichia coli. Proc. Natl. Acad. Sci. U. S. A. 99, 17020–17024.CrossRefPubMedGoogle Scholar
  29. Wertz, J.E., Goldstone, C., Gordon, D.M. and Riley, M.A. (2003) A molecular phylogeny of enteric bacteria and implications for a bacterial species concept. J. Evol. Biol. 16, 1236–1248.CrossRefPubMedGoogle Scholar
  30. Williams, R.J. (1956) Biochemical individuality; the basis for the genetotrophic concept. Wiley, New York.Google Scholar

Copyright information

© Springer Science+Business Media, Inc. 2005

Authors and Affiliations

  1. 1.School of Molecular and Microbial Biosciences G08The University of SydneySydneyAustralia

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