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Mutation discovery in bacterial genomes: metronidazole resistance in Helicobacter pylori


We developed a microarray hybridization–based method, 'comparative genome sequencing' (CGS), to find mutations in bacterial genomes and used it to study metronidazole resistance in H. pylori. CGS identified mutations in several genes, most likely affecting metronidazole activation, and produced no false positives in analysis of three megabases. We conclude that CGS identifies mutations in bacterial genomes efficiently, should enrich understanding of systems biology and genome evolution, and help track pathogens during outbreaks.

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Figure 1: Diagram of the CGS process.


  1. Nuwaysir, E.F. et al. Genome Res. 12, 1749–1755 (2002).

    CAS  Article  Google Scholar 

  2. Albert, T.J. et al. Nucleic Acids Res. 31, e35 (2003).

    Article  Google Scholar 

  3. Wong, C.W. et al. Genome Res. 14, 398–405 (2004).

    CAS  Article  Google Scholar 

  4. Peek, R.M., Jr. Springer Semin. Immunopathol. 2, 197–215 (2005).

    Article  Google Scholar 

  5. Blaser, M.J. & Atherton, J.C. J. Clin. Invest. 113, 321–333 (2004).

    CAS  Article  Google Scholar 

  6. Goodwin, A. et al. Mol. Microbiol. 28, 383–393 (1998).

    CAS  Article  Google Scholar 

  7. Sisson, G. et al. J. Bacteriol. 182, 5091–5096 (2000).

    CAS  Article  Google Scholar 

  8. Jeong, J.Y. et al. J. Bacteriol. 182, 5082–5090 (2000).

    CAS  Article  Google Scholar 

  9. Tomb, J.F. et al. Nature 388, 539–547 (1997).

    CAS  Article  Google Scholar 

  10. Jeong, J.Y. et al. J. Bacteriol. 183, 5155–5162 (2001).

    CAS  Article  Google Scholar 

  11. Sisson, G. et al. Antimicrob. Agents Chemother. 46, 2116–2123 (2002).

    CAS  Article  Google Scholar 

  12. Ernst, F.D. et al. Microbiology 151, 533–546 (2005).

    CAS  Article  Google Scholar 

  13. Bjorkholm, B. et al. Proc. Natl. Acad. Sci. USA 98, 14607–14612 (2001).

    CAS  Article  Google Scholar 

  14. Grogan, D.W., Carver, G.T. & Drake, J.W. Proc. Natl. Acad. Sci. USA 98, 7928–7933 (2001).

    CAS  Article  Google Scholar 

  15. Kell, D.B. Curr. Opin. Microbiol. 7, 296–307 (2004).

    CAS  Article  Google Scholar 

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We thank P. Hoffman, X. Pan and S. Weissman for stimulating discussions. This research was supported by the US National Institutes of Health grants RO1 AI38166, RO1 DK63041, R21 AI057713 and P30 DK52574.

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Correspondence to Thomas J Albert or Douglas E Berg.

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T.J.A., J.E.N., T.A.R., M.M., J.S. and R.D.G. are paid employees of NibleGen Systems Inc.

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Albert, T., Dailidiene, D., Dailide, G. et al. Mutation discovery in bacterial genomes: metronidazole resistance in Helicobacter pylori. Nat Methods 2, 951–953 (2005).

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