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Bacterial DNA topoisomerases are essential enzymes in prokaryotes that regulate DNA topology by introducing transient single- or double-strand breaks in DNA, enabling processes such as replication, transcription, recombination, and chromosomal segregation[1][3][7][9]. The major subtypes in bacteria include type IA (topoisomerase I) and type IIA (DNA gyrase and topoisomerase IV)[2][3][4][6]. DNA gyrase introduces negative supercoils into DNA and is unique to bacteria, while topoisomerase IV mainly decatenates replicated DNA[2][3]. These enzymes are well-validated therapeutic targets for antibacterial agents, notably quinolones and aminocoumarins[2][4][6]. Resistance to these drugs can arise via mutations in topoisomerase genes[6]. Novel classes of inhibitors, such as NBTIs and bisbenzimidazoles, are being developed to overcome resistance, with several showing selectivity for bacterial over human topoisomerases[2][4][8].
Inhibition of DNA supercoiling by stabilizing DNA-enzyme cleavage complexes (for quinolones) - ATPase inhibition in type IIA topoisomerases - Interference with DNA re-ligation leading to double-stranded DNA breaks
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