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.
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References
Bergthorsson, U. and Ochman, H. (1998) Distribution of chromosome length variation in natural isolates of Escherichia coli. Mol. Biol. Evol. 15, 6–16.
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.
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.
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.
Feil, E.J. (2004) Small change: Keeping pace with microevolution. Nature Reviews Microbiology 2, 483–495.
Fiehn, O. (2001) Combining genomics, metabolome analysis and molecular modelling to understand metabolic networks. Comp. Funct. Genom. 2, 155–168.
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.
Hartl, D.L. and Dykhuizen, D.E. (1984) The population genetics of Escherichia coli. Annu. Rev. Genet. 18, 31–68.
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.
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.
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.
Mahon, P. and Dupree, P. (2001) Quantitative and reproducible two-dimensional gel analysis using phoretix 2d full. Electrophoresis 22, 2075–2085.
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.
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.
Ochman, H. and Selander, R.K. (1984) Standard reference strains of Escherichia coli from natural populations. J. Bacteriol. 157, 690–693.
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.
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.
Postgate, J. (1994) The outer reaches of life. Cambridge University Press, Cambridge.
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.
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.
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.
Rock, C.L., Lampe, J.W. and Patterson, R.E. (2000) Nutrition, genetics, and risks of cancer. Annu. Rev. Public Health 21, 47–64.
Sauer, U. (2004) High-throughput phenomics: Experimental methods for mapping fluxomes. Curr. Opin. Biotech. 15, 58–63.
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.
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.
Vaidyanathan, S. (2005) Profiling microbial metabolomes: What do we stand to gain? Metabolomics 1, 17–28.
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.
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.
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.
Williams, R.J. (1956) Biochemical individuality; the basis for the genetotrophic concept. Wiley, New York.
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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.
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Maharjan, R.P., Ferenci, T. Metabolomic diversity in the species Escherichia coli and its relationship to genetic population structure. Metabolomics 1, 235–242 (2005). https://doi.org/10.1007/s11306-005-0002-2
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DOI: https://doi.org/10.1007/s11306-005-0002-2