Insertion of Mini-IS 605 and Deletion of Adjacent Sequences in the Nitroreductase ( rdxA ) Gene Cause Metronidazole Resistance in Helicobacter pylori NCTC11637

We found that NCTC11637, the type strain ofHelicobacter 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 inrdxA (gene HP0954 in the full genome sequence ofH. 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 (por γδαβ), RecA (recA ), or superoxide dismutase (sodB ). This is in accord with another recent study that attributed metronidazole resistance to point mutations inrdxA . However, the mechanism ofrdxA inactivation that we found in NCTC11637 is itself also novel: insertion of mini-IS605 , one of the endogenous transposable elements ofH. pylori , and deletion of adjacent DNA sequences including 462 bp of the 851-bp-longrdxA gene.