Metronidazole is the drug of choice for Bacteroides fragilis infections. It is selectively toxic to anaerobes because:
- A Anaerobes lack thymidylate synthase, making them unable to repair drug-induced DNA breaks
- B Aerobic bacteria inactivate metronidazole via their catalase enzyme
- C Its nitro group is reduced to cytotoxic intermediates only in low-redox (anaerobic) environments, generating free radicals that damage DNA ✓
- D Metronidazole requires activation by a mitochondrial enzyme absent in aerobes
Correct answer: C. Its nitro group is reduced to cytotoxic intermediates only in low-redox (anaerobic) environments, generating free radicals that damage DNA
Explanation
Metronidazole is a prodrug; in anaerobic and microaerophilic organisms, low-potential electron carriers (ferredoxin, flavodoxin) reduce its nitro group to hydroxylamine and nitro-radical intermediates. These reactive species covalently crosslink DNA strands, inhibiting replication and repair. In aerobic cells, oxygen prevents reduction of the nitro group, so toxic intermediates are not generated — explaining selective anaerobic toxicity.
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.