Fluoroquinolones exert bactericidal activity by inhibiting which bacterial enzyme, and what is the consequence of inhibiting this enzyme?

• A RNA polymerase; preventing mRNA transcription
• B Dihydrofolate reductase; preventing tetrahydrofolate synthesis
• C DNA ligase; preventing resealing of nicks during replication
• D DNA gyrase (topoisomerase II) and topoisomerase IV; trapping the enzyme-DNA cleavage complex, causing lethal double-strand breaks ✓

Explanation

Fluoroquinolones inhibit bacterial type II topoisomerases — primarily DNA gyrase (negative supercoiling, essential for gram-negative bacteria) and topoisomerase IV (decatenation, essential for gram-positives). They stabilise the cleaved enzyme-DNA complex, converting the enzyme into a cellular toxin that causes double-strand DNA breaks and triggers the SOS response leading to cell death. Rifampicin targets RNA polymerase, trimethoprim targets DHFR, and no clinically used antibiotic targets DNA ligase.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.