Nowadays, the emergence and the transmission of multidrug-resistant pathogenic bacteria are a severe menace mounting a lot of pressure on the healthcare systems worldwide. Many severe outbreaks of bacterial infections have been reported worldwide in recent years. Thus, there is an immediate demand to develop antibiotics. Some riboswitches are potential targets for overcoming bacterial resistance. This paper demonstrates the bacteriostatic effect of an antisense oligonucleotide (ASO) engineered to suppress the growth of pathogenic bacteria such as Listeria monocytogenes by targeting the Thiamine Pyrophosphate (TPP) riboswitch. It does not inhibit the growth of the conditional pathogenic bacteria Escherichia coli, as it lacks the TPP riboswitch, showing the specificity of action of our ASO. It is covalently bonded with the cell-penetrating protein pVEC. We did bioinformatics analyses of the thiamine pyrophosphate riboswitch regarding its role in synthesizing the metabolite thiamine pyrophosphate, which is essential for bacteria. L. monocytogenes is intrinsically resistant to cephalosporins and usually is treated with ampicillin. A dosage of ASO has been established that inhibits 80% of bacterial growth at 700 nM (4.5 μg/mL). Thus, the TPP riboswitch is a valuable antibacterial target.

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The development of novel antibiotics is becoming a real emergency due to the growing number of multidrug-resistant pathogenic bacteria. This is also a global problem due to mass production and application of various antibiotics both in human and veterinary medicine. Therefore, we need not only to create novel antibiotics but also to speed up the development pipeline. This may be achieved by using novel targets for antibacterial drug discovery. In this review, we focus our attention on several different types of RNA molecules that have been used as antibacterial drug targets. The RNA is the most ambiguous biopolymer in the cell, which carries many different functions. For instance, tRNAs, rRNAs, and mRNAs are essential for gene expression both in the pro-and eukaryotes. However, all these types of RNAs have sequences and something 3D structures that are specific for bacteria only and can be used to shut down essential biochemical processes in bacteria only. All these features make RNA very potent target for antibacterial drug development.

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