Evidence map›Paper›PMID 32347931›Full record

ArticleNucleic acids research2020

Peptides containing the PCNA interacting motif APIM bind to the β-clamp and inhibit bacterial growth and mutagenesis.

Aina Nedal, Synnøve B Ræder, Bjørn Dalhus, Emily Helgesen, Rune J Forstrøm, Kim Lindland, Balagra K Sumabe, Jacob H Martinsen, Birthe B Kragelund, Kirsten Skarstad and 2 more

Open access · goldAbstract read
In one paragraph

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.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
3.6field-weighted citation impact, top 7% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

15 citing papers in PubMed, 26 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors at 3 institutions in 2 countries.

Aina NedalDepartment of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, NTNU, 7489 Trondheim, Norway.
Synnøve B RæderDepartment of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, NTNU, 7489 Trondheim, Norway.
Bjørn DalhusDepartment of Medical Biochemistry, Institute for Clinical Medicine, Oslo University Hospital and University of Oslo, 0424 Oslo, Norway.
Emily HelgesenDepartment of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, NTNU, 7489 Trondheim, Norway.
Rune J ForstrømDepartment of Microbiology, Oslo University Hospital, and University of Oslo, 0424, Oslo, Norway.
Kim LindlandDepartment of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, NTNU, 7489 Trondheim, Norway.
Balagra K SumabeDepartment of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, NTNU, 7489 Trondheim, Norway.
Jacob H MartinsenDepartment of Biology, University of Copenhagen, Ole Maaloes Vej 5, 2200, Copenhagen N, Denmark.
Birthe B KragelundDepartment of Biology, University of Copenhagen, Ole Maaloes Vej 5, 2200, Copenhagen N, Denmark.
Kirsten SkarstadDepartment of Microbiology, Oslo University Hospital, and University of Oslo, 0424, Oslo, Norway.
Magnar BjøråsDepartment of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, NTNU, 7489 Trondheim, Norway.
Marit OtterleiDepartment of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, NTNU, 7489 Trondheim, Norway.
Norwegian University of Science and Technology · NOOslo University Hospital · NOUniversity of Copenhagen · DK

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

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.

Indexed as

AnimalsAnti-Bacterial AgentsDNA-Directed DNA PolymeraseDNA Polymerase IIIDNA ReplicationFemaleMethicillin-Resistant Staphylococcus aureusMice, Inbred BALB CMutagenesisNucleic Acid Synthesis InhibitorsPeptidesProliferating Cell Nuclear AntigenProtein Interaction Domains and MotifsStaphylococcal Skin InfectionsStaphylococcus epidermidisAnti-Bacterial Agentsbeta subunit, DNA polymerase IIIDNA-Directed DNA PolymeraseDNA Polymerase IIINucleic Acid Synthesis InhibitorsPeptidesProliferating Cell Nuclear Antigen

Identifiers

PMID32347931
PMCPMC7261172
OpenAlexW3019317196

What OpenQuestion holds

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Registered trials

None linked

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.