Insertion of mini-IS605 and deletion of adjacent sequences in the nitroreductase (rdxA) gene cause metronidazole resistance in Helicobacter pylori NCTC11637

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 resi...

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Bibliographic Details
Published in:Antimicrobial agents and chemotherapy 1999-11, Vol.43 (11), p.2657-2662
Main Authors: DEBETS-OSSENKOPP, Y. J, POT, R. G. J, VAN WESTERLOO, D. J, GOODWIN, A, VANDENBROUCKE-GRAULS, C. M. J. E, BERG, D. E, HOFFMAN, P. S, KUSTERS, J. G
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Antibiotics. Antiinfectious agents. Antiparasitic agents
Antifungal agents
Bacterial Proteins - genetics
Base Sequence
Biological and medical sciences
Drug Resistance, Microbial
Gene Deletion
Helicobacter pylori
Helicobacter pylori - drug effects
Helicobacter pylori - genetics
Mechanisms of Resistance
Medical sciences
Membrane Proteins - genetics
Metronidazole - pharmacology
Molecular Sequence Data
Mutation - genetics
Mutation - physiology
Nitroreductases - genetics
Oligonucleotide Probes
Pharmacology. Drug treatments
Polymorphism, Restriction Fragment Length
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Summary: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 (porgammadeltaalphabeta), 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.
ISSN:0066-4804
1098-6596
DOI:10.1128/aac.43.11.2657