ArticleNucleic acids research2021
Global RNA profiles show target selectivity and physiological effects of peptide-delivered antisense antibiotics.
Article in Nucleic acids research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed.
- Tobramycin-Peptide Nucleic Acids Synergize with Polymyxin B and Other Bioactive Compounds to Inhibit Growth of Gram-Negative Bacteria.ACS infectious diseases · 2026Article
- A systematic identification of resistance determinants to antisense antibiotics suggests adaptation strategies dependent on the delivery peptide.Nature communications · 2026Article
- Peptide Nucleic Acids (PNAs) in Antimicrobial Therapy: A Next Generation Strategy.International journal of molecular sciences · 2026Review
- Multimodal molecular mechanisms of octanoic acid (OA) against recurrent mastitis causing pathogens.Applied microbiology and biotechnology · 2026Article
- Developing antisense oligomer biotics "asobiotics" as precision antibacterials: designs, strategies, and considerations for future success.FEMS microbiology reviews · 2026Review
- Synthesis of Hydroxamate-Type Siderophores and Their Conjugates with PNA for Evaluation of Iron Binding and Bacterial Uptake.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Mechanistic Studies of Antibacterial PNAs by RNA-Seq Analysis.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Transient analysis and engineering of bacterial metabolic pathways using cell-penetrating peptide-peptide nucleic acid conjugates.Microbial cell factories · 2025Article
- Aminoglycoside-Peptide Nucleic Acid (PNA) Conjugates against Gram-Negative Bacteria.Bioconjugate chemistry · 2025Article
- Antibacterial activities of novel peptide nucleic acids targetingMolecular therapy. Nucleic acids · 2025Article
- Article
- High-Throughput Tiling of Essential mRNAs Increases Potency of Antisense Antibiotics.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Article
- RNA toehold switch-based reporter assay to assess bacterial uptake of antisense oligomers.mBio · 2025Article
- ASOBIOTICS 2024: an interdisciplinary symposium on antisense-based programmable RNA antibiotics.RNA (New York, N.Y.) · 2025Article
- Article
- RNA interactome of hypervirulent Klebsiella pneumoniae reveals a small RNA inhibitor of capsular mucoviscosity and virulence.Nature communications · 2024Article
- Identifying Cell-Penetrating Peptides for Effectively Delivering Antimicrobial Molecules intoAntibiotics (Basel, Switzerland) · 2024Article
- A (metaphorical) moment for RNA-based biotechnology? : Current metaphors for RNA limit development of and public communication about RNA-based technologies.EMBO reports · 2024Article
- A comparative analysis of peptide-delivered antisense antibiotics using diverse nucleotide mimics.RNA (New York, N.Y.) · 2024Article
Corrections and comments
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Authors and funding
6 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Antisense peptide nucleic acids (PNAs) inhibiting mRNAs of essential genes provide a straight-forward way to repurpose our knowledge of bacterial regulatory RNAs for development of programmable species-specific antibiotics. While there is ample proof of PNA efficacy, their target selectivity and impact on bacterial physiology are poorly understood. Moreover, while antibacterial PNAs are typically designed to block mRNA translation, effects on target mRNA levels are not well-investigated. Here, we pioneer the use of global RNA-seq analysis to decipher PNA activity in a transcriptome-wide manner. We find that PNA-based antisense oligomer conjugates robustly decrease mRNA levels of the widely-used target gene, acpP, in Salmonella enterica, with limited off-target effects. Systematic analysis of several different PNA-carrier peptides attached not only shows different bactericidal efficiency, but also activation of stress pathways. In particular, KFF-, RXR- and Tat-PNA conjugates especially induce the PhoP/Q response, whereas the latter two additionally trigger several distinct pathways. We show that constitutive activation of the PhoP/Q response can lead to Tat-PNA resistance, illustrating the utility of RNA-seq for understanding PNA antibacterial activity. In sum, our study establishes an experimental framework for the design and assessment of PNA antimicrobials in the long-term quest to use these for precision editing of microbiota.
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