Helicobacter pylori DNA gyrase and DNA (GyrA/GyrB/DNA)

Helicobacter pylori DNA gyrase and DNA are essential molecular targets for the treatment of H. pylori infections, which are major drivers of chronic gastritis, peptic ulcers, and gastric adenocarcinoma (nih.gov, 2.1.1, 2.4.1). DNA gyrase is a type II topoisomerase composed of GyrA and GyrB subunits that manages DNA topology by introducing negative supercoils, a process vital for DNA replication and transcription (uniprot.org, 2.2.2). Notably, H. pylori lacks a separate topoisomerase IV, making its DNA gyrase the sole enzyme responsible for both supercoiling and chromosome decatenation (nih.gov, 2.3.1, 2.4.1). Fluoroquinolone antibiotics, such as levofloxacin and moxifloxacin, target this enzyme by stabilizing the DNA-gyrase cleavage complex, which halts replication and induces lethal double-strand breaks (nih.gov, 2.3.1, 2.4.4). Simultaneously, the bacterial DNA itself serves as a target for nitroimidazole drugs like metronidazole, which are reduced within the bacterium to form reactive radicals that cause direct DNA strand breaks and helical destabilization (General Pharmacology). The clinical efficacy of targeting these molecules is increasingly challenged by the emergence of resistance, primarily through point mutations in the quinolone resistance-determining region (QRDR) of GyrA or mutations in nitroreductase genes (nih.gov, 2.2.1, 2.4.1).

Other names

Helicobacter pylori DNA gyraseH. pylori topoisomerase IIBacterial DNA (Helicobacter pylori)GyrA/GyrB complex

Inhibition of DNA gyrase activity via stabilization of cleavage complexes and induction of DNA strand breaks through reactive radical formation (nih.gov, 2.3.1, 2.4.4).