## Mechanism of Action of Fluoroquinolones **Key Point:** Fluoroquinolones exert their bactericidal activity by inhibiting bacterial DNA gyrase (topoisomerase II) and topoisomerase IV, enzymes essential for DNA replication, transcription, and repair. ### Molecular Target - **DNA Gyrase**: Introduces negative supercoils into bacterial DNA; primary target in gram-negative bacteria - **Topoisomerase IV**: Decatenates daughter DNA molecules after replication; primary target in gram-positive bacteria - Both enzymes are inhibited by fluoroquinolone binding, leading to accumulation of DNA breaks and cell death ### Why This Matters **High-Yield:** The dual targeting of these topoisomerases explains the broad-spectrum activity and bactericidal (not bacteriostatic) nature of fluoroquinolones, distinguishing them from other antimicrobials. ### Result of Inhibition 1. Accumulation of DNA breaks 2. Impaired DNA replication and transcription 3. Bacterial cell death (bactericidal effect) 4. Concentration-dependent killing **Clinical Pearl:** This mechanism is unique among commonly used antibiotics and explains why fluoroquinolones are effective against both gram-positive and gram-negative organisms, as well as intracellular pathogens. [cite:KD Tripathi 8e Ch 48]
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