Fluoroquinolones inhibit two topoisomerases. In gram-negative organisms, the primary target leading to bactericidal activity is:

• A Topoisomerase IV (decatenation of daughter chromosomes)
• B DNA gyrase (topoisomerase II) — introduces negative supercoils ✓
• C Topoisomerase I — relaxes positive supercoils
• D Topoisomerase III — involved in sister-chromosome separation

Explanation

In gram-negative bacteria, the primary target of fluoroquinolones is DNA gyrase (bacterial topoisomerase II), which introduces negative supercoils necessary for replication and transcription; inhibition creates lethal double-strand DNA breaks. In gram-positive organisms, topoisomerase IV is the primary target. This differential primary targeting explains differences in resistance mutation profiles across species.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.