Which enzyme is the primary target of fluoroquinolone antibiotics?

Explanation

## Mechanism of Action of Fluoroquinolones ### Primary Target Enzymes **Key Point:** Fluoroquinolones inhibit **bacterial DNA gyrase (topoisomerase II)** and **topoisomerase IV**, which are essential for bacterial DNA replication and transcription. ### Detailed Mechanism 1. **DNA Gyrase (Topoisomerase II)** - Introduces negative supercoils into bacterial DNA - Essential for DNA compaction and replication - Primary target in **Gram-negative bacteria** (e.g., *E. coli*, *Pseudomonas*) 2. **Topoisomerase IV** - Relieves positive supercoiling during DNA replication - Separates daughter DNA strands - Primary target in **Gram-positive bacteria** (e.g., *Staphylococcus*, *Streptococcus*) ### Bactericidal Action Fluoroquinolones are **bactericidal** (not bacteriostatic) because enzyme inhibition leads to: - DNA strand breaks - Impaired DNA replication - Cell death **High-Yield:** The differential targeting of DNA gyrase vs. topoisomerase IV explains why different fluoroquinolones have varying activity against Gram-positive vs. Gram-negative organisms. Newer fluoroquinolones (moxifloxacin, gemifloxacin) have enhanced Gram-positive coverage due to better topoisomerase IV inhibition. **Mnemonic:** **GYRASE = Gram-negative** (DNA gyrase is the primary target in Gram-negative bacteria); **TOPO IV = Gram-positive** (topoisomerase IV is the primary target in Gram-positive bacteria). **Clinical Pearl:** Resistance to fluoroquinolones develops through mutations in the genes encoding these enzymes (*gyrA*, *gyrB*, *parC*, *parE*), which is why fluoroquinolone resistance in *Mycobacterium tuberculosis* and *Pseudomonas aeruginosa* is clinically significant.