Riboswitches as new antibiotics targets

Abstract

New cellular targets are needed to reinvigorate antibacterial drug discovery. This need could potentially be filled by riboswitches—messenger RNA (mRNA) structures that regulate gene expression in bacteria. Riboswitches are unique from other RNAs that serve as drug targets in that they have evolved to form structured and highly selective receptors for small drug‐like metabolites. In most cases, metabolite binding to the receptor represses the expression of the gene or genes coded by the mRNA. If a new metabolite analog were designed that binds to the receptor, the gene(s) regulated by that riboswitch could be repressed, with a potentially lethal effect to the bacteria. Recent work suggests that certain antibacterial compounds discovered decades ago function at least in part by targeting riboswitches. Herein we will summarize the experiments validating riboswitches as drug targets, describe the existing technology for riboswitch drug discovery, and discuss the challenges that may face riboswitch drug discoverers.