Spontaneous Mutations That Confer Antibiotic Resistance in Helicobacter pylori


American Society for Microbiology


In this study, we systematically examined in vitro frequencies and spectra of the spontaneous mutations in Helicobacter pylori that confer resistance to clarithromycin (Clar), metronidazole (Mtzr), amoxicillin (Amxr), ciprofloxacin (Cipr), and rifampin (Rifr). The mutation rate of Rifr or Cipr determined in a fluctuation assay is 1 × 10−8 to 2 × 10−8 per cell per division. In contrast, the mutation rates of Clar, Mtzr, and Amxr are much lower (<10−9). However, Mtzr mutants could be readily selected in vitro by using the serial passage method, suggesting that the mutagenic effect and selective effect of a sublethal dose of metronidazole contribute to the rapid development of Mtzr. Analysis of spontaneous Rifr, Clar, and Cipr mutants confirmed previous results indicating that mutations within the rpoB gene, the 23S rRNA gene, and the gyrA gene, respectively, are responsible; also, several new mutant alleles were identified. Mtzr mutants resulted most frequently, but not always, from mutations in the rdxA gene. DNA fragments containing each mutant allele could readily transform susceptible H. pylori strains to resistance, confirming that each mutant allele is responsible for the resistance phenotype.

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