Evidence map›Paper›PMID 34450639›Full record

ArticleThe Journal of antimicrobial chemotherapy2021

Antisense inhibition of the Escherichia coli NrdAB aerobic ribonucleotide reductase is bactericidal due to induction of DNA strand breaks.

Christopher Campion, Godefroid Charbon, Thomas T Thomsen, Peter E Nielsen, Anders Løbner-Olesen

Open access · bronzeAbstract read
In one paragraph

Article in The Journal of antimicrobial chemotherapy, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
0.4field-weighted citation impact, top 41% 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

5 citing papers in PubMed, 7 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Selected strategies to fight pathogenic bacteria.Journal of enzyme inhibition and medicinal chemistry · 2023
    Review
  5. Article
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

5 authors at 1 institution in 1 country.

Christopher CampionDepartment of Cellular and Molecular Medicine, Faculty of Health Sciences, Center for Peptide-Based Antibiotics, The Panum Institute, University of Copenhagen, Blegdamsvej 3c, 2200 Copenhagen N, Denmark.
Godefroid CharbonDepartment of Biology, Faculty of Science, Section for Functional Genomics, University of Copenhagen, Ole Maaløes Vej 5, 2200 Copenhagen N, Denmark.
Thomas T ThomsenDepartment of Biology, Faculty of Science, Section for Functional Genomics, University of Copenhagen, Ole Maaløes Vej 5, 2200 Copenhagen N, Denmark.ORCID 0000-0003-3130-2784
Peter E NielsenDepartment of Cellular and Molecular Medicine, Faculty of Health Sciences, Center for Peptide-Based Antibiotics, The Panum Institute, University of Copenhagen, Blegdamsvej 3c, 2200 Copenhagen N, Denmark.
Anders Løbner-OlesenDepartment of Biology, Faculty of Science, Section for Functional Genomics, University of Copenhagen, Ole Maaløes Vej 5, 2200 Copenhagen N, Denmark.
University of Copenhagen · DK

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundAntisense peptide nucleic acids (PNAs) constitute an alternative to traditional antibiotics, by their ability to silence essential genes.

objectivesTo evaluate the antibacterial effects of antisense PNA-peptide conjugates that target the gene encoding the alpha subunit (NrdA) of the Escherichia coli ribonucleotide reductase (RNR).

methodsBacterial susceptibility of a series of NrdA-targeting PNAs was studied by MIC determination and time-kill analysis. Western-blot analysis, gene complementation and synergy with hydroxyurea were employed to determine the efficiency of NrdA-PNA antisense treatment. The effect on chromosome replication was addressed by determining the DNA synthesis rate, by flow cytometry analysis, by quantitative PCR and by fluorescence microscopy. The use of DNA repair mutants provided insight into the bactericidal action of NrdA-PNA.

resultsTreatment with NrdA-PNA specifically inhibited growth of E. coli, as well as NrdA protein translation at 4 μM. Also, the DNA synthesis rate was reduced, preventing completion of chromosome replication and resulting in formation of double-stranded DNA breaks and cell death.

conclusionsThese data present subunits of the NrdAB RNR as a target for future antisense microbial agents and provide insight into the bacterial physiological response to RNR-targeting antimicrobials.

Indexed as

Peptide Nucleic AcidsRibonucleotide ReductasesAnti-Bacterial AgentsDNAEscherichia coliAnti-Bacterial AgentsDNAPeptide Nucleic AcidsRibonucleotide Reductases

Identifiers

PMID34450639
PMCPMC8521395
OpenAlexW3194893902

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.