ArticleNucleic acids research2020
Peptides containing the PCNA interacting motif APIM bind to the β-clamp and inhibit bacterial growth and mutagenesis.
Article in Nucleic acids research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 26 citations in OpenAlex.
- The RecBCD complex interacts directly with the DNA sliding clamp in Escherichia coli.Nucleic acids research · 2026Article
- A dual-mechanism antimicrobial peptide with antimutagenic activity targets the replisome and induces cell envelope stress.mSphere · 2025Article
- X-ray crystal structure of proliferating cell nuclear antigen 1 from Aeropyrum pernix.Acta crystallographica. Section F, Structural biology communications · 2024Article
- The bacterial DNA sliding clamp, β-clamp: structure, interactions, dynamics and drug discovery.Cellular and molecular life sciences : CMLS · 2024Review
- SOS genes are rapidly induced while translesion synthesis polymerase activity is temporally regulated.Frontiers in microbiology · 2024Article
- RecF protein targeting to post-replication (daughter strand) gaps II: RecF interaction with replisomes.Nucleic acids research · 2023Article
- Activation of multiple stress responses inFrontiers in microbiology · 2023Article
- Review
- Halogenated Pyrrolopyrimidines with Low MIC onAntibiotics (Basel, Switzerland) · 2022Article
- Biotherapeutic effect of cell-penetrating peptides against microbial agents: a review.Tissue barriers · 2022Review
- Bacteriophage Twort protein Gp168 is a β-clamp inhibitor by occupying the DNA sliding channel.Nucleic acids research · 2021Article
- Activating the Cpx response induces tolerance to antisense PNA delivered by an arginine-rich peptide inMolecular therapy. Nucleic acids · 2021Article
- Nucleoside Analogues Are Potent Inducers of Pol V-mediated Mutagenesis.Biomolecules · 2021Article
- Broad-Spectrum Antibacterial Peptide Kills Extracellular and Intracellular Bacteria Without Affecting Epithelialization.Frontiers in microbiology · 2021Article
- Novel Peptides Targeting the β-Clamp Rapidly Kill Planktonic and BiofilmFrontiers in microbiology · 2021Article
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In the fight against antimicrobial resistance, the bacterial DNA sliding clamp, β-clamp, is a promising drug target for inhibition of DNA replication and translesion synthesis. The β-clamp and its eukaryotic homolog, PCNA, share a C-terminal hydrophobic pocket where all the DNA polymerases bind. Here we report that cell penetrating peptides containing the PCNA-interacting motif APIM (APIM-peptides) inhibit bacterial growth at low concentrations in vitro, and in vivo in a bacterial skin infection model in mice. Surface plasmon resonance analysis and computer modeling suggest that APIM bind to the hydrophobic pocket on the β-clamp, and accordingly, we find that APIM-peptides inhibit bacterial DNA replication. Interestingly, at sub-lethal concentrations, APIM-peptides have anti-mutagenic activities, and this activity is increased after SOS induction. Our results show that although the sequence homology between the β-clamp and PCNA are modest, the presence of similar polymerase binding pockets in the DNA clamps allows for binding of the eukaryotic binding motif APIM to the bacterial β-clamp. Importantly, because APIM-peptides display both anti-mutagenic and growth inhibitory properties, they may have clinical potential both in combination with other antibiotics and as single agents.
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