Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Brief Communication
  • Published:

Mutation discovery in bacterial genomes: metronidazole resistance in Helicobacter pylori

Abstract

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.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Diagram of the CGS process.

Similar content being viewed by others

References

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

    Article  CAS  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).

    Article  CAS  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).

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

Download references

Acknowledgements

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.

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Thomas J Albert or Douglas E Berg.

Ethics declarations

Competing interests

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

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Cite this article

Albert, T., Dailidiene, D., Dailide, G. et al. Mutation discovery in bacterial genomes: metronidazole resistance in Helicobacter pylori. Nat Methods 2, 951–953 (2005). https://doi.org/10.1038/nmeth805

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nmeth805

This article is cited by

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing