Small Size, Big Impact: Bacterial Functional Nucleic Acids and Their Applications

Genome mining efforts carried out across diverse bacterial genomes over the past two decades have paid off handsomely, leading to the discovery of a plethora of regulatory RNAs. These RNAs include riboswitches—a class of ligand responsive gene regulating elements—and small RNAs (sRNA)—short RNA or protein targeting sequences. Together, this ensemble of RNAs orchestrates and fine-tunes metabolic, stress response, and virulence pathways. These RNAs are key players in genetic networks. Searches for novel regulatory RNAs and their subsequent characterization remain an exciting area of research. Due to the ingenuity of their design and important functions they execute, recent research has also focused on engineering synthetic mimics of naturally occurring riboswitches and sRNAs and exploring these elements as potential therapeutics. In this chapter, we will present an overview on the discovery, general properties, and key functions of riboswitches and sRNAs annotated in different bacterial genomes. We will examine these RNAs as possible targets for novel antimicrobials. We will also discuss efforts in creating synthetic riboswitches and sRNAs, as well as the possibility of using them in biotechnology and as ammunition in our continued fight against multidrug-resistant pathogens.