Issue 5, 2024

Inhibition of bacterial RNA polymerase function and protein–protein interactions: a promising approach for next-generation antibacterial therapeutics

Abstract

The increasing prevalence of multidrug-resistant pathogens necessitates the urgent development of new antimicrobial agents with innovative modes of action for the next generation of antimicrobial therapy. Bacterial transcription has been identified and widely studied as a viable target for antimicrobial development. The main focus of these studies has been the discovery of inhibitors that bind directly to the core enzyme of RNA polymerase (RNAP). Over the past two decades, substantial advancements have been made in understanding the properties of protein–protein interactions (PPIs) and gaining structural insights into bacterial RNAP and its associated factors. This has led to the crucial role of computational methods in aiding the identification of new PPI inhibitors to affect the RNAP function. In this context, bacterial transcriptional PPIs present promising, albeit challenging, targets for the creation of new antimicrobials. This review will succinctly outline the structural foundation of bacterial transcription networks and provide a summary of the known small molecules that target transcription PPIs.

Graphical abstract: Inhibition of bacterial RNA polymerase function and protein–protein interactions: a promising approach for next-generation antibacterial therapeutics

Article information

Article type
Review Article
Submitted
07 ဒီ 2023
Accepted
25 မတ် 2024
First published
26 မတ် 2024

RSC Med. Chem., 2024,15, 1471-1487

Inhibition of bacterial RNA polymerase function and protein–protein interactions: a promising approach for next-generation antibacterial therapeutics

J. Ye, C. H. Kan, X. Yang and C. Ma, RSC Med. Chem., 2024, 15, 1471 DOI: 10.1039/D3MD00690E

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