DNA sequence analysis of rdxA and frxA from paired metronidazole-sensitive and -resistant Helicobacter pylori isolates obtained from patients with heteroresistance.

Genomic variations of rdxA and frxA genes in eight pairs of metronidazole (MTZ)-sensitive and -resistant isolates of Helicobacter pylori were investigated. The paired strains from each single biopsy had identical lspA-glmM restriction fragment length polymorphism profiles, and the differences in MTZ susceptibility were mostly accounted for by mutations in the rdxA gene. Truncation of RdxA is associated with a minimum inhibitory concentration of 64-128 mg/L. Early truncation of FrxA was observed both in susceptible and resistant isolates of seven paired strains. Inactivation of frxA might play a significant role only in one low-level MTZ-resistant isolate where a missense mutation was found in the rdxA gene.