Bacterial DNA-dependent RNA polymerase (RNAP) (RNAP)

Bacterial DNA-dependent RNA polymerase (RNAP) is the central enzyme of transcription, responsible for the synthesis of all RNA molecules in the cell using DNA as a template (UniProt, 2023). In the Acinetobacter baumannii–calcoaceticus complex, which includes several highly opportunistic and often multi-drug resistant (MDR) pathogens, RNAP is a vital target for antimicrobial intervention (Clinical Microbiology Reviews, 2008). The enzyme is a large, multi-subunit complex, with the beta subunit (encoded by the rpoB gene) serving as the primary binding site for the rifamycin class of antibiotics (Cell, 2001). Drugs like rifampicin bind within the DNA-RNA hybrid binding site, sterically blocking the elongation of the RNA chain and effectively halting bacterial gene expression (StatPearls, 2023). While rifampicin is frequently used in combination therapies to treat Acinetobacter infections, its use is challenged by the rapid emergence of resistance-conferring mutations in the rpoB gene (Antimicrobial Agents and Chemotherapy, 2003). Understanding the structural nuances of RNAP in this specific bacterial complex is essential for the design of novel inhibitors that can bypass existing resistance mechanisms and provide effective treatment for life-threatening nosocomial infections (Clinical Microbiology Reviews, 2008).

Other names

DNA-directed RNA polymeraseRNA polymeraseTranscriptaserpoB (beta subunit)rpoC (beta-prime subunit)

Inhibition of bacterial transcription by binding to the beta subunit of the DNA-dependent RNA polymerase, thereby physically blocking the elongation of the nascent RNA chain (Cell, 2001; StatPearls, 2023).