Engineering Antisense Oligonucleotides as Antibacterial Agents That Target FMN Riboswitches and Inhibit the Growth of Staphylococcus aureus , Listeria monocytogenes , and Escherichia coli .
Martina TraykovskaRobert PenchovskyPublished in: ACS synthetic biology (2022)
In the past several decades, antibiotic drug resistance has emerged as a significant challenge in modern medicine due to the rise of many bacterial pathogenic strains resistant to all known antibiotics. At the same time, riboswitches have emerged as novel targets for antibacterial drug discovery. Here for the first time, we describe the design and applications of antisense oligonucleotides as antibacterial agents that target a riboswitch. The antisense oligonucleotides are covalently coupled with two different cell-penetrating peptides, penetrating Gram-positive and Gram-negative bacterial cells. We specifically target Flavin MonoNucleotide (FMN) riboswitches in Staphylococcus aureus , Listeria monocytogenes , and Escherichia coli that control both synthesis and import of FMN precursors. We have established an average antibiotic dosage by antisense oligonucleotides that inhibit 80% of bacterial growth at 700 nM (4.5 μg/mL). Furthermore, the antisense oligonucleotides do not exhibit toxicity in human cell lines at this concentration. The results demonstrate that riboswitches are suitable targets in antisense technology for antibacterial drug development.
Keyphrases
- nucleic acid
- listeria monocytogenes
- escherichia coli
- gram negative
- staphylococcus aureus
- multidrug resistant
- silver nanoparticles
- drug discovery
- biofilm formation
- induced apoptosis
- anti inflammatory
- essential oil
- oxidative stress
- single cell
- stem cells
- photodynamic therapy
- cell death
- mesenchymal stem cells
- cell proliferation
- pseudomonas aeruginosa
- bone marrow