Bacterial DNA gyrase and topoisomerase IV (Bacillus anthracis) (DNA gyrase/Topo IV)

Bacterial DNA gyrase and topoisomerase IV are essential Type II topoisomerases in Bacillus anthracis that manage DNA topology during replication and transcription [4, 11]. DNA gyrase, a heterotetramer of GyrA and GyrB, introduces negative supercoils to relieve torsional stress ahead of the replication fork [4, 21]. Topoisomerase IV, composed of ParC (GrlA) and ParE (GrlB), is primarily responsible for decatenating daughter chromosomes to allow for proper segregation during cell division [1, 11]. These enzymes are the primary targets of fluoroquinolone antibiotics like ciprofloxacin, which is the standard treatment for anthrax [2, 8]. The drugs work by trapping the enzyme-DNA complex, creating a physical barrier that leads to permanent DNA strand breaks and rapid bacterial death [3, 13]. Resistance typically develops through specific mutations in the subunits' quinolone resistance-determining regions (QRDR), which impair drug binding [1, 4, 9].

Other names

Type II topoisomerasesGyrA/GyrBParC/ParEGrlA/GrlBDNA topoisomerase (ATP-hydrolyzing)

Inhibition of DNA synthesis and induction of cell death by stabilizing the covalent enzyme-DNA cleavage complex (interfacial inhibition), which prevents DNA religation and leads to lethal double-strand breaks [2, 3, 13].