Helicobacter pylori DNA gyrase

Helicobacter pylori DNA gyrase is an essential type II topoisomerase that manages the topological state of the bacterial genome during replication, transcription, and recombination [7, 9]. Unlike most other bacteria, H. pylori lacks topoisomerase IV (ParC/ParE), making DNA gyrase the sole enzyme responsible for both introducing negative supercoils and decatenating interlinked daughter chromosomes [4, 5, 14]. The enzyme exists as a heterotetramer (A2B2) composed of two GyrA subunits, which facilitate DNA cleavage and rejoining, and two GyrB subunits, which provide energy through ATP hydrolysis [1, 6]. It is the primary target for fluoroquinolone antibiotics, such as levofloxacin and moxifloxacin, which are critical components of rescue therapies for H. pylori eradication [2, 8, 10]. These drugs stabilize the covalent gyrase-DNA cleavage complex, leading to permanent double-strand breaks that inhibit DNA synthesis and cause cell death [6, 14]. However, the clinical efficacy of these treatments is significantly hindered by the high prevalence of resistance, primarily caused by point mutations in the quinolone resistance-determining region (QRDR) of the gyrA gene, such as at positions Asn87 and Asp91 [3, 4, 13].

Other names

DNA gyraseGyrA/GyrB complexType II topoisomeraseHelicobacter pylori DNA gyrase / topoisomerase IV

Fluoroquinolones inhibit DNA gyrase by binding to the enzyme-DNA complex at the DNA cleavage site, stabilizing the covalent cleavable complex and preventing the ligation of double-strand breaks, which leads to the inhibition of DNA replication and bacterial cell death [6, 9, 14].