Mutation discovery in bacterial genomes: metronidazole resistance in Helicobacter pylori.
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.
Albert
Thomas J
TJ
NimbleGen Systems Inc., One Science Court, Madison, Wisconsin 53711, USA. talbert@nimblegen.com
Dailidiene
Daiva
D
Dailide
Giedrius
G
Norton
Jason E
JE
Kalia
Awdhesh
A
Richmond
Todd A
TA
Molla
Michael
M
Singh
Jaz
J
Green
Roland D
RD
Berg
Douglas E
DE
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
D000890:Anti-Infective Agents; D001426:Bacterial Proteins; D004269:DNA, Bacterial; D008795:Metronidazole