Riboswitch-based antibacterial drug discovery using high-throughput screening methods

Introduction: Bacterial riboswitches are structured RNA domains usually residing at the 5' untranslated region of messenger RNAs that can directly bind specific metabolites. They serve as logic gates regulating gene expression. As a result, riboswitches enable mRNAs to regulate their own expression without the need for any regulatory proteins. The first riboswitches were found just 10 years ago. Over the last decade, more than dozen different riboswitch classes were identified in many bacterial species, and their number is still growing. These findings indicate that bacteria widely use RNA switches to sense changes in cell physiology and to regulate metabolic pathways. Areas covered: The authors discuss the main mechanisms for riboswitch control of gene expression in bacteria. Various riboswitch classes were found in human bacterial pathogens to control the synthesis of essential cell metabolites as discussed in this review. Some riboswitches can be used as novel targets for antibacterial drug discovery. This review presents the current and possible future high-throughput screening approaches for targeting riboswitches in the process of drug development. Expert opinion: Bacterial riboswitches of 17 different classes are discovered in 36 human bacterial pathogens that can be targeted for addressing the ever-growing need for new antibiotics. In this regard, the adaptation of various in silico, in vitro, and in vivo high-throughput screening methods for probing specific RNA switches are crucial for the success of antibacterial drug discovery process.