Evidence map›Paper›PMID 37306577›Full record

ArticleMicrobiology spectrum2023

Repurposing High-Throughput Screening Identifies Unconventional Drugs with Antibacterial and Antibiofilm Activities against Pseudomonas aeruginosa under Experimental Conditions Relevant to Cystic Fibrosis.

Giovanni Di Bonaventura, Veronica Lupetti, Andrea Di Giulio, Maurizio Muzzi, Alessandra Piccirilli, Lisa Cariani, Arianna Pompilio

Open access · goldAbstract read
In one paragraph

Article in Microbiology spectrum, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed, 1 pooled it
4.4field-weighted citation impact, top 5% 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

20 citing papers in PubMed, 1 synthesis or guideline pooled it, 17 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Review
  4. Article
  5. Article
  6. Revisiting the Fight AgainstAntibiotics (Basel, Switzerland) · 2026
    Review
  7. Article
  8. Article
  9. Fingolimod potentiates minocycline against multidrug-resistantFrontiers in cellular and infection microbiology · 2026
    Article
  10. Review
  11. Review
  12. Review
  13. Carmofur Exhibits Antimicrobial Activity AgainstAntibiotics (Basel, Switzerland) · 2025
    Article
  14. Biotherapeutic potential of different fractions of cell-free supernatants fromFrontiers in cellular and infection microbiology · 2025
    Article
  15. Effect of 5-fluorouracil onFrontiers in microbiology · 2025
    Review
  16. Busulfan inhibitsFrontiers in cellular and infection microbiology · 2025
    Article
  17. Article
  18. FTY720 Reduces the Biomass of Biofilms inAntibiotics (Basel, Switzerland) · 2024
    Article
  19. 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

7 authors at 4 institutions in 1 country.

Giovanni Di BonaventuraDepartment of Medical, Oral, and Biotechnological Sciences, G. d'Annunzio University of Chieti-Pescara, Chieti, Italy.ORCID 0000-0001-5850-2810
Veronica LupettiDepartment of Medical, Oral, and Biotechnological Sciences, G. d'Annunzio University of Chieti-Pescara, Chieti, Italy.
Andrea Di GiulioDepartment of Science, University Roma Tre, Rome, Italy.
Maurizio MuzziDepartment of Science, University Roma Tre, Rome, Italy.
Alessandra PiccirilliDepartment of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy.ORCID 0000-0001-7560-5221
Lisa CarianiMicrobiology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
Arianna PompilioDepartment of Medical, Oral, and Biotechnological Sciences, G. d'Annunzio University of Chieti-Pescara, Chieti, Italy.ORCID 0000-0002-6309-6981
University of Chieti-Pescara · ITRoma Tre University · ITFondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico · ITUniversity of L'Aquila · IT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Pseudomonas aeruginosa is the most common pathogen infecting cystic fibrosis (CF) lungs, causing acute and chronic infections. Intrinsic and acquired antibiotic resistance allow P. aeruginosa to colonize and persist despite antibiotic treatment, making new therapeutic approaches necessary. Combining high-throughput screening and drug repurposing is an effective way to develop new therapeutic uses for drugs. This study screened a drug library of 3,386 drugs, mostly FDA approved, to identify antimicrobials against P. aeruginosa under physicochemical conditions relevant to CF-infected lungs. Based on the antibacterial activity, assessed spectrophotometrically against the prototype RP73 strain and 10 other CF virulent strains, and the toxic potential evaluated toward CF IB3-1 bronchial epithelial cells, five potential hits were selected for further analysis: the anti-inflammatory and antioxidant ebselen, the anticancer drugs tirapazamine, carmofur, and 5-fluorouracil, and the antifungal tavaborole. A time-kill assay showed that ebselen has the potential to cause rapid and dose-dependent bactericidal activity. The antibiofilm activity was evaluated by viable cell count and crystal violet assays, revealing carmofur and 5-fluorouracil as the most active drugs in preventing biofilm formation regardless of the concentration. In contrast, tirapazamine and tavaborole were the only drugs actively dispersing preformed biofilms. Tavaborole was the most active drug against CF pathogens other than P. aeruginosa, especially against Burkholderia cepacia and Acinetobacter baumannii, while carmofur, ebselen, and tirapazamine were particularly active against Staphylococcus aureus and B. cepacia. Electron microscopy and propidium iodide uptake assay revealed that ebselen, carmofur, and tirapazamine significantly damage cell membranes, with leakage and cytoplasm loss, by increasing membrane permeability.

Indexed as

Cystic FibrosisPseudomonas InfectionsAnti-Bacterial AgentsBiofilmsBoron CompoundsBridged Bicyclo Compounds, HeterocyclicDrug RepositioningFluorouracilHigh-Throughput Screening AssaysHumansIsoindolesOrganoselenium CompoundsPseudomonas aeruginosaTirapazamineAnti-Bacterial AgentsBoron CompoundsBridged Bicyclo Compounds, HeterocyclicebselenFluorouracilIsoindolesOrganoselenium CompoundstavaboroleTirapazamineantibacterialantibiofilmantibiotic resistancebiofilmscystic fibrosisdrug repurposingPseudomonas aeruginosa

Identifiers

PMID37306577
PMCPMC10433973
OpenAlexW4380290620

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.