Metronidazole is effective against anaerobes and protozoa but not aerobes. This selective toxicity is dependent on which specific feature of anaerobic organisms?

• A Anaerobes and protozoa possess low-potential electron transport proteins (ferredoxins/flavodoxins) with sufficiently negative redox potential to donate electrons to metronidazole's nitro group, generating cytotoxic radical anion intermediates ✓
• B Anaerobes lack catalase and superoxide dismutase, making them unable to detoxify metronidazole free radicals
• C Aerobic bacteria actively export metronidazole via NorA efflux pump while anaerobes lack this pump
• D Anaerobic cell membranes are more permeable to metronidazole due to absence of ergosterol and cholesterol in the lipid bilayer

Explanation

Metronidazole is a prodrug requiring reductive activation. Its 5-nitro group must be reduced to form a radical anion (NO2 → NO2•−) inside the organism. This reduction requires electron transfer from intracellular electron carriers with sufficiently negative redox potential (Eo' below -200 mV). Anaerobic bacteria and protozoa (Trichomonas, Giardia, Entamoeba) contain ferredoxin or ferredoxin-like proteins (Eo' ≈ -300 to -420 mV) that can reduce the nitro group. Aerobic bacteria maintain high oxygen levels that continuously re-oxidize these electron carriers, preventing metronidazole activation. The activated radical anion covalently binds DNA (breaking strands), RNA, and proteins causing cell death. Resistance often involves acquisition of altered ferredoxin or overexpression of rdxA/frxA gene mutations.

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

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