Evidence map›Paper›PMID 39571043›Full record

ArticlePLoS pathogens2024

Diclofenac sensitizes multi-drug resistant Acinetobacter baumannii to colistin.

Fabiana Bisaro, Clay D Jackson-Litteken, Jenna C McGuffey, Anna J Hooppaw, Sophie Bodrog, Leila Jebeli, Manon Janet-Maitre, Juan C Ortiz-Marquez, Tim van Opijnen, Nichollas E Scott and 2 more

Abstract read
In one paragraph

Article in PLoS pathogens, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing 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

6 citing papers in PubMed.

  1. Review
  2. Antimicrobial Resistance: The Answers.British journal of biomedical science · 2026
    Review
  3. Mechanistic Evaluation of LolA andInternational journal of microbiology · 2026
    Article
  4. Antivirulence drugs against Acinetobacter baumannii: where do they stand?World journal of microbiology & biotechnology · 2025
    Review
  5. Review
  6. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

12 authors.

Fabiana BisaroDepartment of Molecular Microbiology, Washington University School of Medicine in St. Louis; St. Louis, Missouri, United States of America.
Clay D Jackson-LittekenDepartment of Molecular Microbiology, Washington University School of Medicine in St. Louis; St. Louis, Missouri, United States of America.
Jenna C McGuffeyDepartment of Molecular Microbiology, Washington University School of Medicine in St. Louis; St. Louis, Missouri, United States of America.
Anna J HooppawDepartment of Molecular Microbiology, Washington University School of Medicine in St. Louis; St. Louis, Missouri, United States of America.
Sophie BodrogBiology Department, Boston College; Chestnut Hill, Massachusetts, United States of America.
Leila JebeliDepartment of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity, University of Melbourne; Melbourne, Australia.
Manon Janet-MaitreDepartment of Molecular Microbiology, Washington University School of Medicine in St. Louis; St. Louis, Missouri, United States of America.
Juan C Ortiz-MarquezBiology Department, Boston College; Chestnut Hill, Massachusetts, United States of America.
Tim van OpijnenBoston Children's Hospital, Division of Infectious Diseases, Harvard Medical School, Boston, Massachusetts, United States of America.
Nichollas E ScottDepartment of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity, University of Melbourne; Melbourne, Australia.
Gisela Di VenanzioDepartment of Molecular Microbiology, Washington University School of Medicine in St. Louis; St. Louis, Missouri, United States of America.ORCID 0000-0003-1969-3145
Mario F FeldmanDepartment of Molecular Microbiology, Washington University School of Medicine in St. Louis; St. Louis, Missouri, United States of America.ORCID 0000-0003-4497-0976

Funding

Phenylacetic acid catabolism, a novel stress-response pathway in Acinetobacter baumanniiR01AI166359 · NIAID · WASHINGTON UNIVERSITY · PI Mario Feldman · 2022 to 2026
$3.2M
A priori adaptive evolution predictions for antibiotic resistance through genome-wide network analyses and machine learningR01AI148470 · NIAID · BOSTON COLLEGE · PI ORTIZ-MARQUEZ, JUAN CESAR FEDERICO, VAN OPIJNEN, TIM · 2020 to 2024
$2.0M
NIAID NIH HHS R01 AI148470NIAID NIH HHS R01 AI166359
6 · The paper itself

Abstract

Acinetobacter baumannii causes life-threatening infections that are becoming difficult to treat due to increasing rates of multi-drug resistance (MDR) among clinical isolates. This has led the World Health Organization and the CDC to categorize MDR A. baumannii as a top priority for the research and development of new antibiotics. Colistin is the last-resort antibiotic to treat carbapenem-resistant A. baumannii. Not surprisingly, reintroduction of colistin has resulted in the emergence of colistin-resistant strains. Diclofenac is a non-steroidal anti-inflammatory drug used to treat pain and inflammation associated with arthritis. In this work, we show that diclofenac sensitizes colistin-resistant A. baumannii clinical strains to colistin in vitro and in a murine model of pneumonia. Diclofenac also reduced the colistin minimal inhibitory concentration (MIC) of Klebsiella pneumoniae and Pseudomonas aeruginosa isolates. Transcriptomic and proteomic analyses revealed an upregulation of oxidative stress-related genes and downregulation of type IV pili induced by the combination treatment. Notably, the concentrations of colistin and diclofenac effective in the murine model were substantially lower than those determined in vitro, implying a stronger synergistic effect in vivo compared to in vitro. A pilA mutant strain, lacking the primary component of the type IV pili, became sensitive to colistin in the absence of diclofenac. This suggest that the downregulation of type IV pili is key for the synergistic activity of these drugs in vivo and indicates that colistin and diclofenac exert an anti-virulence effect. Together, these results suggest that diclofenac can be repurposed with colistin to treat MDR A. baumannii.

Indexed as

Acinetobacter baumanniiAcinetobacter InfectionsAnti-Bacterial AgentsColistinDiclofenacDrug Resistance, Multiple, BacterialAnimalsAnti-Inflammatory Agents, Non-SteroidalDisease Models, AnimalDrug SynergismHumansMiceMicrobial Sensitivity TestsAnti-Bacterial AgentsAnti-Inflammatory Agents, Non-SteroidalColistinDiclofenac

Identifiers

PMID39571043
PMCPMC11620633

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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.