Evidence map›Paper›PMID 34244523›Full record

ArticleNPJ biofilms and microbiomes2021

Identification of small molecules that interfere with c-di-GMP signaling and induce dispersal of Pseudomonas aeruginosa biofilms.

Jens Bo Andersen, Louise Dahl Hultqvist, Charlotte Uldahl Jansen, Tim Holm Jakobsen, Martin Nilsson, Morten Rybtke, Jesper Uhd, Blaine Gabriel Fritz, Roland Seifert, Jens Berthelsen and 4 more

Open access · goldAbstract read
In one paragraph

Article in NPJ biofilms and microbiomes, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.

0numbers the graph read from it
0cells of the map it votes in
43citing papers in PubMed
4.4field-weighted citation impact, top 4% 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

43 citing papers in PubMed, 69 citations in OpenAlex.

  1. Review
  2. Review
  3. Biofilms: from the cradle of life to life support.NPJ biofilms and microbiomes · 2026
    Review
  4. UnderstandingMicroorganisms · 2026
    Review
  5. BioMed research international · 2026
    Review
  6. Review
  7. Article
  8. Review
  9. Review
  10. Article
  11. Exploring aggregation genes in aJournal of bacteriology · 2025
    Article
  12. Anti-Biofilm Agents to OvercomePharmaceuticals (Basel, Switzerland) · 2025
    Review
  13. Review
  14. Article
  15. Beyond Antibiotics: What the Future Holds.Antibiotics (Basel, Switzerland) · 2024
    Review
  16. Review
  17. Review
  18. Article
  19. High efficacy treatment of murineAntimicrobial agents and chemotherapy · 2024
    Article
  20. 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

14 authors at 3 institutions in 3 countries.

Jens Bo AndersenCosterton Biofilm Center. Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.ORCID 0000-0003-1720-1581
Louise Dahl HultqvistCosterton Biofilm Center. Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Charlotte Uldahl JansenDepartment of Chemistry, Technical University of Denmark, Lyngby, Denmark.ORCID 0000-0002-1168-8002
Tim Holm JakobsenCosterton Biofilm Center. Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.ORCID 0000-0002-1671-2155
Martin NilssonCosterton Biofilm Center. Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Morten RybtkeCosterton Biofilm Center. Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.ORCID 0000-0002-6218-6774
Jesper UhdDepartment of Chemistry, Technical University of Denmark, Lyngby, Denmark.ORCID 0000-0003-4638-9587
Blaine Gabriel FritzCosterton Biofilm Center. Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.ORCID 0000-0002-2085-894X
Roland SeifertInstitute of Pharmacology and Research Core Unit Metabolomics, Hannover Medical School Carl-Neuberg-Straße 1, Hannover, Germany.
Jens BerthelsenCosterton Biofilm Center. Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Thomas Eiland NielsenCosterton Biofilm Center. Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.ORCID 0000-0001-8700-1951
Katrine QvortrupDepartment of Chemistry, Technical University of Denmark, Lyngby, Denmark.ORCID 0000-0003-3828-2069
Michael GivskovCosterton Biofilm Center. Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. mgivskov@sund.ku.dk.
Tim Tolker-NielsenCosterton Biofilm Center. Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. ttn@sund.ku.dk.ORCID 0000-0002-9751-474X
University of Copenhagen · DKTechnical University of Denmark · DKMedizinische Hochschule Hannover · DE

Funding

Translational Research Center to Expedite Novel Therapies in Cystic FibrosisP30DK089507 · NIDDK · SEATTLE CHILDREN'S HOSPITAL · PI Christopher Hooper Goss, Lucas R Hoffman · 2010 to 2026
$21.4M
NIDDK NIH HHS P30 DK089507
6 · The paper itself

Abstract

Microbial biofilms are involved in a number of infections that cannot be cured, as microbes in biofilms resist host immune defenses and antibiotic therapies. With no strict biofilm-antibiotic in the current pipelines, there is an unmet need for drug candidates that enable the current antibiotics to eradicate bacteria in biofilms. We used high-throughput screening to identify chemical compounds that reduce the intracellular c-di-GMP content in Pseudomonas aeruginosa. This led to the identification of a small molecule that efficiently depletes P. aeruginosa for c-di-GMP, inhibits biofilm formation, and disperses established biofilm. A combination of our lead compound with standard of care antibiotics showed improved eradication of an implant-associated infection established in mice. Genetic analyses provided evidence that the anti-biofilm compound stimulates the activity of the c-di-GMP phosphodiesterase BifA in P. aeruginosa. Our work constitutes a proof of concept for c-di-GMP phosphodiesterase-activating drugs administered in combination with antibiotics as a viable treatment strategy for otherwise recalcitrant infections.

Indexed as

AnimalsAnti-Bacterial AgentsBiofilmsChromatography, High Pressure LiquidCyclic GMPDose-Response Relationship, DrugDrug DiscoveryGene Expression ProfilingGene Expression Regulation, BacterialHigh-Throughput Nucleotide SequencingMicePseudomonas aeruginosaSignal TransductionTandem Mass SpectrometryTranscriptomeAnti-Bacterial Agentsbis(3',5')-cyclic diguanylic acidCyclic GMP

Identifiers

PMID34244523
PMCPMC8271024
OpenAlexW3177999222

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

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.