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 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.
Debets-Ossenkopp
Y J
YJ
Department of Medical Microbiology, Faculty of Medicine, Vrije Universiteit, Amsterdam, The Netherlands.
Pot
R G
RG
van Westerloo
D J
DJ
Goodwin
A
A
Vandenbroucke-Grauls
C M
CM
Berg
D E
DE
Hoffman
P S
PS
Kusters
J G
JG
D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000235:genetics*; D001483:Base Sequence; D004352:Drug Resistance, Microbial; D017353:Gene Deletion; D016480:Helicobacter pylori / Q000187:drug effects* / Q000235:genetics*; D008565:Membrane Proteins / Q000235:genetics*; D008795:Metronidazole / Q000494:pharmacology*; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics / Q000502:physiology*; D009601:Nitroreductases / Q000235:genetics*; D015345:Oligonucleotide Probes; D012150:Polymorphism, Restriction Fragment Length
D001426:Bacterial Proteins; D008565:Membrane Proteins; D015345:Oligonucleotide Probes; D008795:Metronidazole; C077236:RdxA protein, Rhodobacter sphaeroides; D009601:Nitroreductases