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Antimicrobial Agents and Chemotherapy, November 2000, p. 3127-3132, Vol. 44, No. 11
0066-4804/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Mouse-Colonizing Helicobacter pylori SS1 Is Unusually Susceptible to Metronidazole Due to Two Complementary Reductase Activities

Jin-Yong Jeong and Douglas E. Berg*

Departments of Molecular Microbiology and Genetics, Washington University Medical School, St. Louis, Missouri 63110

Received 19 April 2000/Returned for modification 1 July 2000/Accepted 16 August 2000

In most strains of Helicobacter pylori, mutational inactivation of the rdxA (HP0954) gene, which encodes a nitroreductase that converts metronidazole (MTZ) from a harmless prodrug to a mutagenic and bacteriocidal product, is sufficient to make this pathogen resistant to clinically significant levels of MTZ. Here we report that SS1, a strain with the special ability to colonize mice, is unusual in being susceptible to very low concentrations of MTZ (0.5 µg/ml) and in being especially difficult to mutate to MTZ resistance (Mtzr). These phenotypic traits were traced to expression in this strain of the normally quiescent H. pylori frxA gene (HP0642, an rdxA paralog) along with rdxA. Transformation tests using rdxA::cam and frxA::kan insertion mutant DNAs, with selection solely for the chloramphenicol and kanamycin resistance markers, and sequence analyses of frxA in spontaneous Mtzr derivatives of rdxA null mutant strains each showed that the development of Mtzr in SS1 required inactivation of both rdxA and frxA. Inactivation of either gene alone left SS1 susceptible to MTZ, although it was readily mutable from an MTZ-susceptible to an Mtzr phenotype. Reverse transcriptase PCR tests showed that frxA mRNA was at least 10-fold more abundant in SS1 than in reference strain 26695. It is proposed that these reductases play primarily nutritional roles during bacterial growth.

* Corresponding author. Mailing address: Department of Molecular Microbiology, Campus Box 8230, Washington University Medical School, 4566 Scott Ave., St. Louis, MO 63110. Phone: (314) 362-2772. Fax: (314) 362-1232 or (314) 362-3203. E-mail: berg{at}borcim.wustl.edu.

Antimicrobial Agents and Chemotherapy, November 2000, p. 3127-3132, Vol. 44, No. 11
0066-4804/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Latham, S. R., Labigne, A., Jenks, P. J. (2002). Production of the RdxA protein in metronidazole-susceptible and -resistant isolates of Helicobacter pylori cultured from treated mice. J Antimicrob Chemother 49: 675-678 [Abstract] [Full Text]  
  • Kwon, D. H., Hulten, K., Kato, M., Kim, J. J., Lee, M., El-Zaatari, F. A. K., Osato, M. S., Graham, D. Y. (2001). DNA Sequence Analysis of rdxA and frxA from 12 Pairs of Metronidazole-Sensitive and -Resistant Clinical Helicobacter pylori Isolates. Antimicrob. Agents Chemother. 45: 2609-2615 [Abstract] [Full Text]  
  • Latham, S. R., Owen, R. J., Elviss, N. C., Labigne, A., Jenks, P. J. (2001). Differentiation of Metronidazole-Sensitive and -Resistant Clinical Isolates of Helicobacter pylori by Immunoblotting with Antisera to the RdxA Protein. J. Clin. Microbiol. 39: 3052-3055 [Abstract] [Full Text]  
  • Jeong, J.-Y., Mukhopadhyay, A. K., Akada, J. K., Dailidiene, D., Hoffman, P. S., Berg, D. E. (2001). Roles of FrxA and RdxA Nitroreductases of Helicobacter pylori in Susceptibility and Resistance to Metronidazole. J. Bacteriol. 183: 5155-5162 [Abstract] [Full Text]  


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