Resistance to metronidazole was described previously and is predominantly associated with mutations in rdxA (hp0954),
a gene encoding an oxygen-insensitive NAD(P)H nitroreductase (16–19).
Mutations in two additional genes, frxA (hp0642) and frxB (hp1508, encoding a ferredoxin-like enzyme), both of which encode NAD(P)H-flavin oxidoreductases, have been shown to enhance H. pylori resistance when found along with rdxA gene mutations (20–23). However, the precise mechanism of metroni- dazole resistance is still debated, given that metronidazole resis- tance may also arise in H. pylori with mutations in the frxA gene only (22, 24). In addition, it is unclear whether other mutations in genes outside rdxA or frxA are associated with metronidazole re- sistance.