Frameshift mutations in rdxA and metronidazole resistance in North American Helicobacter pylori isolates

In Helicobacter pylori, the oxygen-insensitive nitroreductase RdxA is likel y to activate metronidazole (Mtz) by reduction and formation of cytotoxic i ntermediates. Mutations in rdxA have been associated with Mtz resistance in H. pylori. In vitro Mtz susceptibilities of 17 randomly selected H. pylori isolates were determined by the agar dilution method. DNA sequence analysi s of rdxA alleles of eight susceptible isolates (MIC range: 0.25-1.0 mg/L) and nine resistant isolates (MIC range: 16-256 mg/L) showed that six of nin e Mtz-resistant H. pylori isolates contained insertion or deletion mutation s ('indel' mutations). One isolate contained a substitution mutation at cod on position 148 that resulted in the introduction of a premature stop codon . Creation of stop codons within the rdxA coding sequence by either framesh ift or substitution mutations resulted in premature translation termination and expression of putatively truncated RdxA polypeptides.