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Antimicrobial Agents and Chemotherapy, March 2001, p. 727-733, Vol. 45, No. 3
0066-4804/01/$04.00+0   DOI: 10.1128/AAC.45.3.727-733.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Spontaneous Mutations That Confer Antibiotic Resistance in Helicobacter pylori

Ge Wang, Trevor J. M. Wilson, Qin Jiang, and Diane E. Taylor*

Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, Alberta, Canada

Received 5 September 2000/Returned for modification 15 November 2000/Accepted 7 December 2000

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.

* Corresponding author. Mailing address: Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, Alberta, Canada T6G 2H7. Phone: (780) 492-4777. Fax: (780) 492-7521. E-mail: diane.taylor{at}ualberta.ca.

Antimicrobial Agents and Chemotherapy, March 2001, p. 727-733, Vol. 45, No. 3
0066-4804/01/$04.00+0   DOI: 10.1128/AAC.45.3.727-733.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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