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Related Concept Videos

Types of RNA01:23

Types of RNA

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Overview
Three main types of RNA are involved in protein synthesis: messenger RNA (mRNA), transfer RNA (tRNA), and ribosomal RNA (rRNA). These RNAs perform diverse functions and can be broadly classified as protein-coding or non-coding RNA. Non-coding RNAs play important roles in the regulation of gene expression in response to developmental and environmental changes. Non-coding RNAs in prokaryotes can be manipulated to develop more effective antibacterial drugs for human or animal use.
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Riboswitches01:56

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Riboswitches are non-coding mRNA domains that regulate the transcription and translation of downstream genes without the help of proteins. Riboswitches bind directly to a metabolite and can form unique stem-loop or hairpin structures in response to the amount of the metabolite present. They have two distinct regions – a metabolite-binding aptamer and an expression platform.
The aptamer has high specificity for a particular metabolite which allows riboswitches to specifically regulate...
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Computational design and experimental validation of fast oligonucleotide-sensing allosteric ribozymes with predefined oligonucleotide binding sites.

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Targeting FMN, TPP, SAM-I, and glmS Riboswitches with Chimeric Antisense Oligonucleotides for Completely Rational

Nikolet Pavlova1, Martina Traykovska1, Robert Penchovsky1

  • 1Laboratory of Synthetic Biology and Bioinformatics, Faculty of Biology, Sofia University "St. Kliment Ohridski", 8 Dragan Tzankov Blvd., 1164 Sofia, Bulgaria.

Antibiotics (Basel, Switzerland)
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Summary

Chimeric antisense oligonucleotides targeting bacterial riboswitches offer a novel approach to combatting antibiotic resistance. This method shows efficacy against resistant strains without toxicity to human cells.

Keywords:
antibacterial agentsantibacterial drug discoveryantisense oligonucleotidescell-penetrating peptidesdrug targetsrational drug developmentriboswitches

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Area of Science:

  • Microbiology
  • Molecular Biology
  • Drug Discovery

Background:

  • Antimicrobial drug resistance is a major global health threat.
  • Riboswitches are bacterial mRNA regulatory elements that control gene expression.
  • Targeting riboswitches presents a promising strategy for developing new antibacterial agents.

Purpose of the Study:

  • To describe the rational design and application of chimeric antisense oligonucleotides (ASOs) targeting specific bacterial riboswitches.
  • To evaluate the efficacy and safety of ASOs coupled with cell-penetrating peptides as antibacterial agents.
  • To demonstrate the potential of riboswitches as targets for novel antibiotic development.

Main Methods:

  • Genome-wide bioinformatic analyses to select four key riboswitches (glmS, FMN, TPP, SAM-I).
  • Design and synthesis of chimeric antisense oligonucleotides conjugated with the cell-penetrating oligopeptide pVEC.
  • Testing ASO efficacy against *Staphylococcus aureus*, *Listeria monocytogenes*, and *Escherichia coli*.
  • Assessment of ASO toxicity in human cell lines.

Main Results:

  • ASOs effectively targeted selected riboswitches in Gram-positive and Gram-negative bacteria.
  • An average dosage of 700 nM (4.5 μg/mL) of ASOs inhibited 80% of bacterial growth.
  • No significant toxicity was observed in human cell lines at effective concentrations.
  • Demonstrated suitability of riboswitches as targets for ASO-based antibacterial therapies.

Conclusions:

  • Rational design of chimeric ASOs targeting specific riboswitches is a viable strategy against antibiotic-resistant bacteria.
  • This approach offers a potential for developing narrow or broad-spectrum antibiotics adaptable to emerging resistance.
  • ASO technology targeting riboswitches represents an innovative avenue for next-generation antibacterial treatments.