Bacterial DNA gyrase (target of fluoroquinolones) !

DNA gyrase is a bacteria-only topoisomerase II that introduces negative supercoils; fluoroquinolones block it.

Updated 2026-11-01

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Key facts

A₂B₂ tetramer: GyrA cuts and rejoins DNA (active-site tyrosine); GyrB hydrolyses ATP.
It is the only topoisomerase that introduces negative supercoiling; it relieves the strain ahead of the fork.
Topoisomerase IV (ParC, ParE) unlinks daughter chromosomes at the end of replication.
Fluoroquinolones trap the cut gyrase–DNA complex (and topo IV) → double-strand breaks → bacterial death.
In Gram-negatives the main target is usually gyrase; in Gram-positives, topo IV.

The supercoiling level controls expression of gyrase itself (homeostatic feedback).
Human cells have no gyrase, so the drug is selective, although high concentrations affect human topo II slightly.

Fluoroquinolone resistance arises mainly from mutations in the 'quinolone resistance-determining region' of gyrA and parC, and from efflux pumps.
In multidrug-resistant tuberculosis, fluoroquinolones are second-line drugs; gyrA resistance helps define extensively drug-resistant TB with other criteria.
Class adverse effects: tendinopathy and Achilles tendon rupture, QT prolongation, glucose disturbances; avoided where possible in children and pregnancy.

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What activity is unique to DNA gyrase?

It introduces negative supercoils into DNA using ATP; no human enzyme does this.

How do fluoroquinolones kill bacteria?

They trap the cut gyrase (or topo IV)–DNA complex and create lethal double-strand breaks.

What is the main mechanism of fluoroquinolone resistance?

Mutations in gyrA and parC that weaken drug binding, plus efflux pumps.

Educational information, not medical advice. For any symptom, see a health professional.

Sources: gyrA: DNA gyrase subunit A (Staphylococcus aureus) (UniProt, 2026); 2XCT: The twinned 3.35A structure of S. aureus Gyrase complex with Ciprofloxacin and DNA (RCSB Protein Data Bank, 2026); Ciprofloxacin: MedlinePlus Drug Information (MedlinePlus, US National Library of Medicine, 2026); Textbook of Biochemistry for Medical Students, 6th ed. (Jaypee Brothers Medical Publishers (Vasudevan DM, Sreekumari S, Vaidyanathan K), 2011).

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