Fluoroquinolones exert bactericidal activity by trapping a ternary complex of drug-DNA-enzyme. Which specific event in this mechanism actually leads to bacterial cell death?

• A Direct alkylation of guanine residues in DNA by the quinolone ring
• B The trapped complex prevents DNA replication fork progression, causing replication stress and chromosome fragmentation ✓
• C Inhibition of RNA polymerase sigma factor leading to transcription arrest
• D Cross-linking of the two DNA strands making both strands inaccessible

Explanation

Fluoroquinolones stabilize the DNA gyrase (or topoisomerase IV) cleavage complex, trapping broken DNA strands in a covalently linked drug-enzyme-DNA intermediate. This blocks the DNA replication fork, triggers the SOS repair response, induces reactive oxygen species-dependent pathways, and ultimately results in double-strand DNA breaks and chromosome fragmentation causing cell death. Direct alkylation and RNA polymerase inhibition are not mechanisms of quinolones.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.