Beyond the approved: target sites and inhibitors of bacterial RNA polymerase from bacteria and fungi

Covering: 2016 to 2022RNA polymerase (RNAP) is the central enzyme in bacterial gene expression representing an attractive and validated target for antibiotics. Two well-known and clinically approved classes of natural product RNAP inhibitors are the rifamycins and the fidaxomycins. Rifampicin (Rif), a semi-synthetic derivative of rifamycin, plays a crucial role as a first line antibiotic in the treatment of tuberculosis and a broad range of bacterial infections. However, more and more pathogens such as Mycobacterium tuberculosis develop resistance, not only against Rif and other RNAP inhibitors. To overcome this problem, novel RNAP inhibitors exhibiting different target sites are urgently needed. This review includes recent developments published between 2016 and today. Particular focus is placed on novel findings concerning already known bacterial RNAP inhibitors, the characterization and development of new compounds isolated from bacteria and fungi, and providing brief insights into promising new synthetic compounds.