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.

Access optionsAccess options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

Figure 1: Diagram of the CGS process.

References

  1. 1

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

  2. 2

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

  3. 3

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

  4. 4

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

  5. 5

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

  6. 6

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

  7. 7

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

  8. 8

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

  9. 9

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

  10. 10

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

  11. 11

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

  12. 12

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

  13. 13

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

  14. 14

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

  15. 15

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

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

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

Supplementary Methods (PDF 101 kb)

Supplementary Data (PDF 96 kb)

Rights and permissions

Reprints and Permissions

About this article

Further reading