Evidence map›Paper›PMID 27775002›Full record

ArticleScientific reports2016

Auxotrophy-based High Throughput Screening assay for the identification of Bacillus subtilis stringent response inhibitors.

Liis Andresen, Vallo Varik, Yuzuru Tozawa, Steffi Jimmy, Stina Lindberg, Tanel Tenson, Vasili Hauryliuk

Abstract read
In one paragraph

Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
–field-weighted citation impact
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

16 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
  4. Recent Advances in Bacterial Persistence Mechanisms.International journal of molecular sciences · 2023
    Review
  5. Article
  6. Review
  7. Article
  8. Article
  9. Review
  10. Review
  11. Article
  12. Article
  13. Article
  14. Subinhibitory Concentrations of Bacteriostatic Antibiotics InduceAntimicrobial agents and chemotherapy · 2017
    Article
  15. Article
  16. 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

7 authors.

Liis AndresenDepartment of Molecular Biology, Umeå University, Building 6K, 6L University Hospital Area, SE-901 87 Umeå, Sweden.
Vallo VarikDepartment of Molecular Biology, Umeå University, Building 6K, 6L University Hospital Area, SE-901 87 Umeå, Sweden.
Yuzuru TozawaGraduate School of Science and Engineering, Saitama University, 255 Shimo-Okubo, Sakura-ku, Saitama, Saitama 338-8570, Japan.
Steffi JimmyDepartment of Molecular Biology, Umeå University, Building 6K, 6L University Hospital Area, SE-901 87 Umeå, Sweden.
Stina LindbergLaboratories for Chemical Biology Umeå (LCBU), Department of Chemistry, Umeå University, SE-901 87 Sweden.
Tanel TensonUniversity of Tartu, Institute of Technology, Nooruse 1, 50411 Tartu, Estonia.
Vasili HauryliukDepartment of Molecular Biology, Umeå University, Building 6K, 6L University Hospital Area, SE-901 87 Umeå, Sweden.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The stringent response is a central adaptation mechanism that allows bacteria to adjust their growth and metabolism according to environmental conditions. The functionality of the stringent response is crucial for bacterial virulence, survival during host invasion as well as antibiotic resistance and tolerance. Therefore, specific inhibitors of the stringent response hold great promise as molecular tools for disarming and pacifying bacterial pathogens. By taking advantage of the valine amino acid auxotrophy of the Bacillus subtilis stringent response-deficient strain, we have set up a High Throughput Screening assay for the identification of stringent response inhibitors. By screening 17,500 compounds, we have identified a novel class of antibacterials based on the 4-(6-(phenoxy)alkyl)-3,5-dimethyl-1H-pyrazole core. Detailed characterization of the hit compounds as well as two previously identified promising stringent response inhibitors - a ppGpp-mimic nucleotide Relacin and cationic peptide 1018 - showed that neither of the compounds is sufficiently specific, thus motivating future application of our screening assay to larger and more diverse molecular libraries.

Indexed as

Amino Acids, Branched-ChainAnti-Bacterial AgentsBacillus subtilisBacterial ProteinsDeoxyguanosineDipeptidesDose-Response Relationship, DrugGuanosine TetraphosphateHigh-Throughput Screening AssaysPyrazolesValineAmino Acids, Branched-ChainAnti-Bacterial AgentsBacterial ProteinsDeoxyguanosineDipeptidesGuanosine TetraphosphatePyrazolesrelacinValine

Identifiers

PMID27775002
PMCPMC5075769

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Registered trials

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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.