ArticlePloS one2012
Targeting RNA polymerase primary σ70 as a therapeutic strategy against methicillin-resistant Staphylococcus aureus by antisense peptide nucleic acid.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed.
- Nucleic Acid-Based Antimicrobial Strategies Against Drug-Resistant Staphylococcus aureus: A Review of Mechanisms of Action and Delivery Approaches.Infectious diseases and therapy · 2026Review
- Developing antisense oligomer biotics "asobiotics" as precision antibacterials: designs, strategies, and considerations for future success.FEMS microbiology reviews · 2026Review
- Shelf-life extension of lettuce using cell-penetrating peptide-peptide nucleic acid conjugates targetingCurrent research in food science · 2026Article
- Chemical strategies for antisense antibiotics.Chemical Society reviews · 2024Review
- Promising strategies employing nucleic acids as antimicrobial drugs.Molecular therapy. Nucleic acids · 2024Review
- General and Specific Cytotoxicity of Chimeric Antisense Oligonucleotides in Bacterial Cells and Human Cell Lines.Antibiotics (Basel, Switzerland) · 2024Article
- Combined antimicrobial effect of two peptide nucleic acids againstJournal of veterinary science · 2024Article
- Antisense inhibition of RNA polymerase α subunit ofMicrobiology spectrum · 2023Article
- Subtractive modification of bacterial consortium using antisense peptide nucleic acids.Frontiers in microbiology · 2023Article
- Antimicrobial Activity of Peptide-Coupled Antisense Peptide Nucleic Acids in Streptococcus pneumoniae.Microbiology spectrum · 2022Article
- Amphipathic dendritic poly-peptides carrier to deliver antisense oligonucleotides against multi-drug resistant bacteria in vitro and in vivo.Journal of nanobiotechnology · 2022Article
- Potentiating the Anti-Tuberculosis Efficacy of Peptide Nucleic Acids through Combinations with Permeabilizing Drugs.Microbiology spectrum · 2022Article
- The Non-phosphorylating Glyceraldehyde-3-Phosphate Dehydrogenase GapN Is a Potential New Drug Target inFrontiers in microbiology · 2022Article
- Bacterial Nosocomial Infections: Multidrug Resistance as a Trigger for the Development of Novel Antimicrobials.Antibiotics (Basel, Switzerland) · 2021Review
- Silencing Antibiotic Resistance with Antisense Oligonucleotides.Biomedicines · 2021Review
- Conformational Changes of Anoplin, W-MreBInternational journal of molecular sciences · 2020Article
- Antibacterial Peptide Nucleic Acids-Facts and Perspectives.Molecules (Basel, Switzerland) · 2020Review
- Structure-Guided Designing and Evaluation of Peptides Targeting Bacterial Transcription.Frontiers in bioengineering and biotechnology · 2020Article
- Virulence of methicillin-resistant Staphylococcus aureus modulated by the YycFG two-component pathway in a rat model of osteomyelitis.Journal of orthopaedic surgery and research · 2019Article
- A Novel Peptide Nucleic Acid against the Cytidine Monophosphate Kinase of S. aureus Inhibits Staphylococcal Infection In Vivo.Molecular therapy. Nucleic acids · 2019Article
Corrections and comments
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Authors and funding
8 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundMethicillin-resistant Staphylococcus aureus (MRSA) causes threatening infection-related mortality worldwide. Currently, spread of multi-drug resistance (MDR) MRSA limits therapeutic options and requires new approaches to "druggable" target discovery, as well as development of novel MRSA-active antibiotics. RNA polymerase primary σ⁷⁰ (encoded by gene rpoD) is a highly conserved prokaryotic factor essential for transcription initiation in exponentially growing cells of diverse S. aureus, implying potential for antisense inhibition. METHODOLOGY/PRINCIPAL
findingsBy synthesizing a serial of cell penetrating peptide conjugated peptide nucleic acids (PPNAs) based on software predicted parameters and further design optimization, we identified a target sequence (234 to 243 nt) within rpoD mRNA conserved region 3.0 being more sensitive to antisense inhibition. A (KFF)₃K peptide conjugated 10-mer complementary PNA (PPNA2332) was developed for potent micromolar-range growth inhibitory effects against four pathogenic S. aureus strains with different resistance phenotypes, including clinical vancomycin-intermediate resistance S. aureus and MDR-MRSA isolates. PPNA2332 showed bacteriocidal antisense effect at 3.2 fold of MIC value against MRSA/VISA Mu50, and its sequence specificity was demonstrated in that PPNA with scrambled PNA sequence (Scr PPNA2332) exhibited no growth inhibitory effect at higher concentrations. Also, PPNA2332 specifically interferes with rpoD mRNA, inhibiting translation of its protein product σ⁷⁰ in a concentration-dependent manner. Full decay of mRNA and suppressed expression of σ⁷⁰ were observed for 40 µM or 12.5 µM PPNA2332 treatment, respectively, but not for 40 µM Scr PPNA2332 treatment in pure culture of MRSA/VISA Mu50 strain. PPNA2332 (≥1 µM) essentially cleared lethal MRSA/VISA Mu50 infection in epithelial cell cultures, and eliminated viable bacterial cells in a time- and concentration- dependent manner, without showing any apparent toxicity at 10 µM.
conclusionsThe present result suggested that RNAP primary σ⁷⁰ is a very promising candidate target for developing novel antisense antibiotic to treat severe MRSA infections.
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