Target intelligence / Profile preview

Bacterial DNA and RNA synthesis machinery

Molecular classification
Enzyme, Transcription factor, Other
01

Overview

The bacterial DNA and RNA synthesis machinery is a coordinated system of enzymes and proteins essential for the replication and expression of the bacterial genome [1.1.1, 1.1.2]. This machinery includes the replisome, which carries out DNA replication through the actions of DNA polymerases, helicases, primases, and topoisomerases like DNA gyrase and topoisomerase IV [1.1.2, 1.2.4]. It also includes the transcription complex, centered around DNA-dependent RNA polymerase (RNAP), which synthesizes various RNA species required for protein production [1.1.1, 1.2.1]. These processes are fundamental to bacterial cell division and survival, making them highly effective targets for a wide range of antibiotics [1.1.3, 1.3.1]. Fluoroquinolones, for instance, target topoisomerases to induce lethal DNA strand breaks, while rifamycins bind to RNAP to halt transcription [1.2.1, 1.2.4]. The structural divergence between bacterial and eukaryotic nucleic acid synthesis components provides a basis for selective toxicity in treating infections [1.2.1, 1.3.1]. However, the clinical utility of drugs targeting this machinery is frequently challenged by the emergence of resistance mutations in the genes encoding these enzymes [1.2.1, 1.2.5]. Understanding the structural and functional nuances of this machinery is critical for the development of next-generation antimicrobials to combat multi-drug resistant pathogens [1.1.2, 1.2.5].

Other names
Bacterial nucleic acid synthesis machineryBacterial replication and transcription machineryBacterial replisome and transcription complex
02

Mechanism of action

Inhibition of DNA gyrase and topoisomerase IV to prevent DNA replication; inhibition of DNA-dependent RNA polymerase to block transcription; induction of DNA damage; and inhibition of nucleotide precursor synthesis.

03

Biological functions

DNA replicationTranscriptionCell proliferationCell cycle
04

Disease associations

Infection
05

Safety considerations

Development of antimicrobial resistanceTendonitis and tendon rupture (fluoroquinolones)Hepatotoxicity (rifamycins)Disruption of commensal microbiotaClostridioides difficile-associated diarrhea
06

Interacting drugs

Ciprofloxacin

8 more in the full profile.

07

Biomarkers

rpoB mutation statusgyrA/gyrB mutation statusparC/parE mutation statusBacterial loadMinimum Inhibitory Concentration (MIC)

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