DNA gyrase and Topoisomerase IV in Helicobacter pylori (DNA gyrase/Topoisomerase IV)

DNA gyrase and topoisomerase IV are essential bacterial Type II topoisomerases in Helicobacter pylori that manage DNA supercoiling and decatenation during replication and transcription (PMID: 11159615). DNA gyrase, composed of GyrA and GyrB subunits, introduces negative supercoils into the DNA, while topoisomerase IV, composed of ParC and ParE, is primarily involved in the segregation of daughter chromosomes (UniProt: P56001, O25502). These enzymes are critical therapeutic targets for fluoroquinolone antibiotics like levofloxacin and moxifloxacin, which are frequently used in rescue regimens for H. pylori eradication when first-line therapies fail (PMID: 25631126). The drugs stabilize the covalent enzyme-DNA cleavage complex, preventing DNA religation and resulting in lethal double-strand breaks that lead to bacterial cell death (StatPearls: NBK547740). Resistance is a major clinical concern, typically driven by mutations in the quinolone resistance-determining regions (QRDR) of the gyrA gene, which reduce drug binding affinity (PMID: 30244086). Effective targeting of these enzymes is vital for treating chronic gastritis and reducing the risk of peptic ulcers and gastric adenocarcinoma associated with persistent H. pylori infection (NIH: Genetic and Rare Diseases Information Center).

Other names

DNA gyraseTopoisomerase IVType II topoisomeraseGyrAGyrBParCParEQuinolone resistance-determining region (QRDR)

Fluoroquinolones bind to the DNA gyrase-DNA or topoisomerase IV-DNA complex, trapping the enzyme in a state where the DNA is cleaved but not religated. This stabilization of the cleavable complex blocks the movement of replication forks and RNA polymerase, leading to permanent double-stranded DNA breaks and rapid bacterial cell death (PMID: 11159615, StatPearls: NBK547740).