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Mutation discovery in bacterial genomes: metronidazole resistance in Helicobacter pylori

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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.

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Figure 1: Diagram of the CGS process.

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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.

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Author notes

  1. Awdhesh Kalia

    Present address: Department of Biology, and Center for Genetics and Molecular Medicine, University of Louisville, Louisville, Kentucky, 40292, USA

Authors and Affiliations

  1. NimbleGen Systems Inc., One Science Court, Madison, 53711, Wisconsin, USA

    Thomas J Albert, Jason E Norton, Todd A Richmond, Michael Molla, Jaz Singh & Roland D Green

  2. Departments of Molecular Microbiology, Genetics and Medicine, 8220 McDonnell Pediatric Research Building, Box 8230, Washington University Medical School, St. Louis, 63110, Missouri, USA

    Daiva Dailidiene, Giedrius Dailide, Awdhesh Kalia & Douglas E Berg

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  1. Thomas J Albert
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  2. Daiva Dailidiene
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  4. Jason E Norton
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  9. Roland D Green
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  10. Douglas E Berg
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Correspondence to Thomas J Albert or Douglas E Berg.

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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.

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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). https://doi.org/10.1038/nmeth805

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

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