Metronidazole resistance in Helicobacter pylori is primarily mediated by mutations in which gene encoding an oxygen-insensitive NADPH nitroreductase?

• A 23S rRNA (leading to macrolide cross-resistance)
• B pbp1A (encoding penicillin-binding protein)
• C rdxA (encoding NADPH flavodoxin reductase) ✓
• D gyrA (encoding DNA gyrase A subunit)

Explanation

Metronidazole enters H. pylori and is activated by reduction of its nitro group, primarily by the oxygen-insensitive NADPH flavodoxin reductase encoded by rdxA. Loss-of-function mutations in rdxA (and to a lesser extent frxA) prevent this activation, resulting in metronidazole resistance. This resistance mechanism is specific to the organism's anaerobic activation pathway. Clarithromycin resistance in H. pylori involves 23S rRNA mutations; fluoroquinolone resistance involves gyrA mutations.

Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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