Metronidazole resistance in Helicobacter pylori

Abstract

Modern triple drug regimens are highly effective for treating Helicobacter pylori infection, but bacterial resistance to one of the most effective antibiotics, metronidazole, is a serious and increasing problem. The activity of metronidazole in H. pylori is dependent on reduction of its nitro moiety to highly reactive compounds that cause DNA strand breakage. The acquisition of resistance is highly associated with mutational inactivation of the rdxA gene, which encodes an oxygen-insensitive NADPH nitroreductase. Recent evidence has suggested that inactivation of frxA (NADPH flavin oxidoreductase), fdxB (ferredoxin-like protein) and possibly other reductase-encoding genes may also contribute to the resistant phenotype. Improved understanding of the mechanisms of metronidazole resistance in H. pylori is essential for the development and validation of biopsy-based tests for detection of resistance in clinical practice.