Antibiotic drugs targeting bacterial RNAs

RNAs have diverse structures that include bulges and internal loops able to form tertiary contacts or serve as ligand binding sites. The recent increase in structural and functional information related to RNAs has put them in the limelight as a drug target for small molecule therapy. In addition, the recognition of the marked difference between prokaryotic and eukaryotic rRNA has led to the development of antibiotics that specifically target bacterial rRNA, reduce protein translation and thereby inhibit bacterial growth. To facilitate the development of new antibiotics targeting RNA, we here review the literature concerning such antibiotics, mRNA, riboswitch and tRNA and the key methodologies used for their screening.

Graphical abstractMany antibiotics are known to target ribosomal RNA (rRNA) in prokaryotes to inhibit the growth of bacteria. In order to facilitate the discovery of improved antibiotics targeting RNA, we describe the secondary structures of partial rRNA and indicate the binding sites for tetracycline, puromycin, lincomycin and other antibiotics. With the development of new drug discovery technologies, targeting RNA for better antibiotics is emerging as a new frontier in drug discovery.Figure optionsDownload full-size imageDownload as PowerPoint slide