Riboswitches : A fresh new promise as an anti-bacterial drug targets

There is increasing concern that the current antibacterial drug repertoire includes mainly decades-old chemical scaffolds that target a very narrow spectrum of cellular processes. It is to highlighted that antibiotics drug development has produced only one new chemical scaffold in the past 30 years, and currently prescribed antibiotics collectively disrupt the function of only four bacterial life processes. Perhaps as a consequence, antibiotic resistance is now emerging at an alarmingly rapid pace, with indications that even the most recently approved antibiotics could soon be ineffective. Sustained success in the long-term battle against bacterial pathogens will require the identification of new chemical scaffolds that target other cellular processes. 

One potentially vulnerable process is the regulation of gene expression by metabolite-sensing RNAs called riboswitches.

In many bacteria, the expression of a number of genes crucial to metabolite biosynthesis or transport is regulated by mRNA structures called riboswitches. Typically found in the 5'-untranslated region (5'-UTR) of certain bacterial mRNAs, members of each known riboswitch class form a structured receptor, or 'aptamer', that has evolved to bind to a specific fundamental metabolite. If the cognate metabolite is not present when the 5'-UTR is transcribed, the riboswitch in most cases folds into a structure that does not interfere with the expression of the adjacent open reading frame (ORF). When present at a sufficiently high concentration, the metabolite binds to the riboswitch receptor, which induces the formation of a structure in the nascent mRNA that represses the expression of the ORF. This structure can be a terminator hairpin, which halts RNA synthesis before the ORF can be synthesized or a hairpin that sequesters the Shine-Dalgarno sequence and prevents the ribosome from binding to the mRNA and translating the ORF. Because the gene or group of genes regulated by a riboswitch is usually involved in the synthesis or transport of its cognate metabolite, riboswitches are direct regulators of cellular metabolite concentrations.

In fact, few anti-bacterial drugs previously thought to have a certain mechanism of action are now found to work partly by means of riboswitches. As such riboswitches show a great promise of hope in our fight against the pathogenic microbes. Amen to that.