DNA gyrase and Topoisomerase IV (GyrA/B and ParC/E)

DNA gyrase and topoisomerase IV are essential bacterial Type II topoisomerases that regulate the topological state of DNA during replication, transcription, and recombination (PubMed: 24512483). DNA gyrase is unique in its ability to introduce negative supercoils into DNA, a process required to neutralize the positive supercoiling that accumulates ahead of replication forks (PubMed: 25691586). Topoisomerase IV primarily functions to decatenate interlinked daughter chromosomes following DNA replication, ensuring proper segregation into daughter cells (PubMed: 15105113). While most bacteria possess both enzymes, Mycobacterium tuberculosis is notable for lacking topoisomerase IV; in this pathogen, DNA gyrase performs the functions of both enzymes, making it the sole and indispensable Type II topoisomerase (PubMed: 9623998). These enzymes are the primary targets of the fluoroquinolone class of antibiotics, such as moxifloxacin and levofloxacin, which are critical components of multidrug-resistant tuberculosis (MDR-TB) treatment regimens (PubMed: 21572165). The drugs act by trapping the enzyme in a covalent complex with cleaved DNA, preventing religation and leading to the accumulation of lethal double-strand breaks that result in bacterial cell death (PubChem). Resistance to these drugs typically arises through specific mutations in the gyrA or gyrB genes, which alter the drug-binding pocket and necessitate the use of alternative therapeutic strategies (PubMed: 15105113).

Other names

DNA topoisomerase IIType II topoisomeraseDNA topoisomerase 2-alphaDNA topoisomerase 4Gyrase

Inhibition of DNA religation by stabilizing the enzyme-DNA covalent cleavage complex, leading to lethal double-strand breaks.