title: The Helicobacter pylori mutY homologue HP0142 is an antimutator gene that prevents specific C to A transversions.
abstract: Extensive genetic variability resulting from a high mutation rate and frequent recombination is a characteristic of Helicobacter pylori. Its average mutation rate is 1 x 10(-6), similar to that of Escherichia coli mutator strains. Few genes involved in DNA repair have been functionally characterized in H. pylori. In E. coli, the DNA glycosylase MutY is a part of the base excision repair system. The H. pylori mutY homolog HP0142 was analyzed in this study. HP0142 was disrupted by inserting a kanamycin resistance cassette. Mutation rates were determined by measuring the frequency of point mutations in rpoB conferring resistance against rifampicin. Inactivation of mutY in H. pylori resulted in an increase of the mutation frequency by a factor of up to 34. Sequence analysis of rpoB in rifampicin-resistant clones selected from the mutY mutant showed a modest increase of G:C/T:A transversions in comparison to clones selected from wild type strains. In contrast, inactivation of mutY had a profound impact on the distribution of mutations within rpoB. This finding suggests that the efficiency with which mutY prevents transversions is strongly dependent upon the sequence context. Inactivation of mutY was associated with a stationary phase fitness deficit in competitive cultures with the wild type strain.
authors.affiliation: Department of Medical Microbiology and Hospital Epidemiology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Kulick
authors.forename: Claudia
authors.initials: C
authors.lastname: Moccia
authors.forename: Christian
authors.initials: C
authors.lastname: Kraft
authors.forename: Sebastian
authors.initials: S
authors.lastname: Suerbaum
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology; D045647:DNA Glycosylases / Q000235:genetics / Q000502:physiology*; D053843:DNA Mismatch Repair; D004252:DNA Mutational Analysis; D004269:DNA, Bacterial / Q000378:metabolism; D012321:DNA-Directed RNA Polymerases / Q000235:genetics / Q000378:metabolism; D024881:Drug Resistance, Bacterial / Q000235:genetics; D017353:Gene Deletion; D016480:Helicobacter pylori / Q000235:genetics / Q000502:physiology*; D016254:Mutagenesis, Insertional; D017354:Point Mutation; D012293:Rifampin / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D004269:DNA, Bacterial; D012321:DNA-Directed RNA Polymerases; C105078:RNA polymerase beta subunit; D045647:DNA Glycosylases; C061738:mutY adenine glycosylase; D012293:Rifampin