Target intelligence / Profile preview

Bacterial DNA topoisomerase

Molecular classification
Enzyme, DNA-modifying enzyme, Topoisomerase family
01

Overview

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].

Other names
Bacterial topoisomeraseProkaryotic topoisomeraseDNA gyrase (for type IIA)Topoisomerase IV (for type IIA)Topoisomerase I
02

Mechanism of action

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

03

Biological functions

Regulation of DNA topologyDNA replicationDNA transcriptionDNA recombinationDNA supercoiling control
04

Disease associations

InfectionAntibacterial drug resistance
05

Safety considerations

Potential cytotoxicity in host if selectivity for bacterial topoisomerases is lostDevelopment of bacterial resistance (e.g., mutations in topoisomerase genes)Off-target effects on mitochondrial topoisomerases (rare but possible)
06

Interacting drugs

Fluoroquinolones (e.g., ciprofloxacin, levofloxacin)

4 more in the full profile.

07

Biomarkers

Genetic mutations in gyrA and parC genes (for resistance monitoring)Topoisomerase expression levels (in research)

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