Riboswitches as Antimicrobial Targets

The spread of antibiotic-resistant bacteria represents a substantial health threat contributing to morbidity and mortality worldwide. Current antibiotics act on a few metabolic pathways, facilitating the emergence of resistance to existing antibiotics. Consequently, developing new regulatory inhibition mechanisms capable of acting differently from the current ones becomes an immediate necessity. In this context, riboswitches represent novel and promising targets for developing useful antibacterial drugs. Riboswitches are RNA sensors that affect posttranscriptional processes through their ability to bind to small molecules, such as vitamins, amino acids, and nucleotides. These nucleic acid structures regulate up to 4% of all bacterial genes, many of which are essential for their survival. In this line, this chapter will examine nine suitable classes of riboswitches (flavin mononucleotide (FMN), lysine, MoCo RNA motif, PreQ1, SAM-I, cyclic-di-GMP I and II, glmS, and thiamine pyrophosphate (TPP)) that control a unique and essential biosynthetic pathway. The current state of riboswitch-based drug discovery is discussed, along with their respective structures, cognate ligands, advantages, and limitations.