title: 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.
authors.affiliation: NimbleGen Systems Inc., One Science Court, Madison, Wisconsin 53711, USA. talbert@nimblegen.com
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Albert
authors.forename: Daiva
authors.initials: D
authors.lastname: Dailidiene
authors.forename: Giedrius
authors.initials: G
authors.lastname: Dailide
authors.forename: Jason E
authors.initials: JE
authors.lastname: Norton
authors.forename: Awdhesh
authors.initials: A
authors.lastname: Kalia
authors.forename: Todd A
authors.initials: TA
authors.lastname: Richmond
authors.forename: Michael
authors.initials: M
authors.lastname: Molla
authors.forename: Jaz
authors.initials: J
authors.lastname: Singh
authors.forename: Roland D
authors.initials: RD
authors.lastname: Green
authors.forename: Douglas E
authors.initials: DE
authors.lastname: Berg
mesh_terms: D000890:Anti-Infective Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics*; D004269:DNA, Bacterial / Q000235:genetics; D024881:Drug Resistance, Bacterial; D016680:Genome, Bacterial; D016481:Helicobacter Infections; D016480:Helicobacter pylori / Q000187:drug effects* / Q000235:genetics; D008795:Metronidazole / Q000494:pharmacology*; D009154:Mutation / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D010437:Peptic Ulcer / Q000382:microbiology
chemical_list: D000890:Anti-Infective Agents; D001426:Bacterial Proteins; D004269:DNA, Bacterial; D008795:Metronidazole