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Antimicrobial Agents and Chemotherapy, November 1999, p. 2657-2662, Vol. 43, No. 11
0066-4804/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Insertion of Mini-IS605 and Deletion of Adjacent Sequences in the Nitroreductase (rdxA) Gene Cause Metronidazole Resistance in Helicobacter pylori NCTC11637

Yvette J. Debets-Ossenkopp,1 Raymond G. J. Pot,1 David J. van Westerloo,1 Avery Goodwin,2 Christina M. J. E. Vandenbroucke-Grauls,1 Douglas E. Berg,3 Paul S. Hoffman,2 and Johannes G. Kusters1,*

Department of Medical Microbiology and Infection Control, Faculty of Medicine, Vrije Universiteit, Amsterdam, The Netherlands1; Department of Molecular Microbiology, Washington University, St. Louis, Missouri3; and Department of Microbiology and Immunology, Faculty of Medicine, Dalhousie University, Halifax, Canada2

Received 19 January 1999/Returned for modification 19 April 1999/Accepted 27 August 1999

We found that NCTC11637, the type strain of Helicobacter pylori, the causative agent of peptic ulcer disease and an early risk factor for gastric cancer, is metronidazole resistant. DNA transformation, PCR-based restriction analysis, and DNA sequencing collectively showed that the metronidazole resistance of this strain was due to mutation in rdxA (gene HP0954 in the full genome sequence of H. pylori 26695) and that resistance did not depend on mutation in any of the other genes that had previously been suggested: catalase (katA), ferredoxin (fdx), flavodoxin (fldA), pyruvate:flavodoxin oxidoreductase (porgamma delta alpha beta ), RecA (recA), or superoxide dismutase (sodB). This is in accord with another recent study that attributed metronidazole resistance to point mutations in rdxA. However, the mechanism of rdxA inactivation that we found in NCTC11637 is itself also novel: insertion of mini-IS605, one of the endogenous transposable elements of H. pylori, and deletion of adjacent DNA sequences including 462 bp of the 851-bp-long rdxA gene.

* Corresponding author. Mailing address: Department of Medical Microbiology and Infection Control, Vrije Universiteit Amsterdam, Van der Boechorststraat 7, 1081 BT Amsterdam, The Netherlands. Phone: 31-20-4448319. Fax: 31-20-4448318. E-mail: JG.Kusters.mm{at}med.vu.nl.

Antimicrobial Agents and Chemotherapy, November 1999, p. 2657-2662, Vol. 43, No. 11
0066-4804/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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