ArticleAntimicrobial agents and chemotherapy2012
Bacterial resistance to antisense peptide phosphorodiamidate morpholino oligomers.
Article in Antimicrobial agents and chemotherapy, 2012. 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, 48 citations in OpenAlex.
- A systematic identification of resistance determinants to antisense antibiotics suggests adaptation strategies dependent on the delivery peptide.Nature communications · 2026Article
- A Cell-Penetrating Peptide-Derived Fluorescent Probe for Selective Isolation of Bacterial Spores.Microbial biotechnology · 2026Article
- Shared structural mechanisms of alternating access between the secondary peptide transporter SbmA and ABC transporters.Nature communications · 2026Article
- Developing antisense oligomer biotics "asobiotics" as precision antibacterials: designs, strategies, and considerations for future success.FEMS microbiology reviews · 2026Review
- ASOBIOTICS 2024: an interdisciplinary symposium on antisense-based programmable RNA antibiotics.RNA (New York, N.Y.) · 2025Article
- Antisense phosphorodiamidate morpholino oligomers retain activity inFrontiers in microbiology · 2025Article
- Chemical strategies for antisense antibiotics.Chemical Society reviews · 2024Review
- Peptide nucleic acid conjugates and their antimicrobial applications-a mini-review.European biophysics journal : EBJ · 2023Review
- Mechanism of Action of Ribosomally Synthesized and Post-Translationally Modified Peptides.Chemical reviews · 2022Review
- Antisense Peptide Nucleic Acid-Diaminobutanoic Acid Dendron Conjugates with SbmA-Independent Antimicrobial Activity against Gram-Negative Bacteria.ACS infectious diseases · 2022Article
- Translocation of non-lytic antimicrobial peptides and bacteria penetrating peptides across the inner membrane of the bacterial envelope.Current genetics · 2022Review
- Innovative developments and emerging technologies in RNA therapeutics.RNA biology · 2022Article
- Molecular mechanism of SbmA, a promiscuous transporter exploited by antimicrobial peptides.Science advances · 2021Article
- Silencing Antibiotic Resistance with Antisense Oligonucleotides.Biomedicines · 2021Review
- Nucleic Acid Hybrids as Advanced Antibacterial Nanocarriers.Pharmaceutics · 2020Review
- The Microbial Toxin Microcin B17: Prospects for the Development of New Antibacterial Agents.Journal of molecular biology · 2019Review
- Cardiolipin-Based Lipopolyplex Platform for the Delivery of Diverse Nucleic Acids into Gram-Negative Bacteria.Pharmaceuticals (Basel, Switzerland) · 2019Article
- Rationally designing antisense therapy to keep up with evolving bacterial resistance.PloS one · 2019Article
- Article
- Integrated roles of BclA and DD-carboxypeptidase 1 in Bradyrhizobium differentiation within NCR-producing and NCR-lacking root nodules.Scientific reports · 2017Article
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
Peptide phosphorodiamidate morpholino oligomers (PPMOs) are synthetic DNA mimics that bind cRNA and inhibit bacterial gene expression. The PPMO (RFF)(3)RXB-AcpP (where R is arginine, F, phenylalanine, X is 6-aminohexanoic acid, B is β-alanine, and AcpP is acyl carrier protein) is complementary to 11 bases of the essential gene acpP (which encodes acyl carrier protein). The MIC of (RFF)(3)RXB-AcpP was 2.5 μM (14 μg/ml) in Escherichia coli W3110. The rate of spontaneous resistance of E. coli to (RFF)(3)RXB-AcpP was 4 × 10(-7) mutations/cell division. A spontaneous (RFF)(3)RXB-AcpP-resistant mutant (PR200.1) was isolated. The MIC of (RFF)(3)RXB-AcpP was 40 μM (224 μg/ml) for PR200.1. The MICs of standard antibiotics for PR200.1 and W3110 were identical. The sequence of acpP was identical in PR200.1 and W3110. PR200.1 was also resistant to other PPMOs conjugated to (RFF)(3)RXB or peptides with a similar composition or pattern of cationic and nonpolar residues. Genomic sequencing of PR200.1 identified a mutation in sbmA, which encodes an active transport protein. In separate experiments, a (RFF)(3)RXB-AcpP-resistant isolate (RR3) was selected from a transposome library, and the insertion was mapped to sbmA. Genetic complementation of PR200.1 or RR3 with sbmA restored susceptibility to (RFF)(3)RXB-AcpP. Deletion of sbmA caused resistance to (RFF)(3)RXB-AcpP. We conclude that resistance to (RFF)(3)RXB-AcpP was linked to the peptide and not the phosphorodiamidate morpholino oligomer, dependent on the composition or repeating pattern of amino acids, and caused by mutations in sbmA. The data further suggest that (RFF)(3)R-XB PPMOs may be transported across the plasma membrane by SbmA.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.