Nature Methods 2, 951 - 953 (2005)
Published online: 18 November 2005; | doi:10.1038/nmeth805
Mutation discovery in bacterial genomes: metronidazole resistance in Helicobacter pyloriThomas J Albert1, Daiva Dailidiene2, Giedrius Dailide2, Jason E Norton1, Awdhesh Kalia2, 3, Todd A Richmond1, Michael Molla1, Jaz Singh1, Roland D Green1
& Douglas E Berg21
NimbleGen Systems Inc., One Science Court, Madison, Wisconsin 53711, USA. 2
Departments of Molecular Microbiology, Genetics and Medicine, 8220 McDonnell Pediatric Research Building, Box 8230, Washington University Medical School, St. Louis, Missouri 63110, USA. 3
Present address: Department of Biology, and Center for Genetics and Molecular Medicine, University of Louisville, Louisville, Kentucky 40292, USA.
Correspondence should be addressed to Thomas J Albert talbert@nimblegen.com or Douglas E Berg berg@borcim.wustl.edu 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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