Bacterial DNA-directed RNA polymerase (RNAP)

Bacterial DNA-directed RNA polymerase (RNAP) is the essential multi-subunit enzyme complex responsible for transcribing genetic information from DNA into various forms of RNA, including mRNA, tRNA, and rRNA. The core enzyme typically consists of five subunits (α2ββ'ω), which associate with a sigma (σ) factor to form the holoenzyme capable of promoter-specific initiation (UniProt, P0A8V2). This machinery is a critical target for antimicrobial therapy because its structure and mechanism differ significantly from eukaryotic RNA polymerases, allowing for selective toxicity against bacterial pathogens. Drugs such as the rifamycin class (e.g., rifampin) bind to the β-subunit within the DNA-RNA channel to physically obstruct the growth of the RNA transcript, while others like fidaxomicin target the switch region to inhibit the initial steps of transcription (PubMed, PMID: 22230521). This target is clinically vital for treating infections such as tuberculosis and Clostridioides difficile, though its therapeutic utility is often challenged by the emergence of resistance through point mutations in the rpoB gene (StatPearls, NBK557485).

Other names

Bacterial RNA polymeraseDNA-dependent RNA polymeraseTranscription machineryRNAP complexBacterial RNA synthesis machinery

Inhibition of bacterial DNA-directed RNA polymerase by binding to the beta subunit (rifamycins) or the switch region (fidaxomicin), thereby sterically blocking the elongation of the nascent RNA chain or preventing the transition from transcription initiation to elongation (StatPearls, PMID: 30020613; PubMed, PMID: 21306243).