Mutation discovery in bacterial genomes: metronidazole resistance in Helicobacter pylori

• Published in: Nature methods Vol. 2; no. 12; pp. 951 - 953
• Main Authors: Albert, Thomas J, Berg, Douglas E, Dailidiene, Daiva, Dailide, Giedrius, Norton, Jason E, Kalia, Awdhesh, Richmond, Todd A, Molla, Michael, Singh, Jaz, Green, Roland D
• Format: Journal Article
• Language: English
• Published: United States Nature Publishing Group 01-12-2005
• Subjects: Analysis; Anti-Infective Agents - pharmacology; Bacteria; Bacterial Proteins - genetics; DNA microarrays; DNA, Bacterial - genetics; Drug resistance in microorganisms; Drug Resistance, Bacterial; Gene mutations; Genetic aspects; Genome, Bacterial; Helicobacter Infections; Helicobacter pylori; Helicobacter pylori - drug effects; Helicobacter pylori - genetics; Hybridization; Metronidazole; Metronidazole - pharmacology; Mutation; Mutation - genetics; Oligonucleotide Array Sequence Analysis - methods; Outbreaks; Pathogens; Peptic Ulcer - microbiology; United States
• ISSN: 1548-7091; 1548-7105
• DOI: 10.1038/nmeth805

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.