Evidence map›Paper›PMID 38683873›Full record

ArticlePLoS biology2024

A host-directed oxadiazole compound potentiates antituberculosis treatment via zinc poisoning in human macrophages and in a mouse model of infection.

Alexandra Maure, Emeline Lawarée, Francesco Fiorentino, Alexandre Pawlik, Saideep Gona, Alexandre Giraud-Gatineau, Matthew J G Eldridge, Anne Danckaert, David Hardy, Wafa Frigui and 11 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in PLoS biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. iScience · 2026
    Article
  2. Review
  3. 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

21 authors.

Alexandra MaureInstitut Pasteur, Université Paris Cité, CNRS UMR 6047, Unit for Integrated Mycobacterial Pathogenomics, Paris, France.
Emeline LawaréeInstitut Pasteur, Université Paris Cité, CNRS UMR 6047, Unit for Integrated Mycobacterial Pathogenomics, Paris, France.
Francesco FiorentinoDepartment of Drug Chemistry and Technologies, Sapienza University of Rome, Rome, Italy.
Alexandre PawlikInstitut Pasteur, Université Paris Cité, CNRS UMR 6047, Unit for Integrated Mycobacterial Pathogenomics, Paris, France.
Saideep GonaDepartment of Genetic Medicine, University of Chicago, Chicago, Illinois, United States of America.
Alexandre Giraud-GatineauInstitut Pasteur, Université Paris Cité, CNRS UMR 6047, Biology of Spirochetes Unit, Paris, France.
Matthew J G EldridgeInstitut Pasteur, Université Paris Cité, Chromatine et Infection unit, Paris, France.
Anne DanckaertInstitut Pasteur, Université Paris Cité, UTechS BioImaging-C2RT, Paris, France.
David HardyInstitut Pasteur, Université Paris Cité, Histopathology Platform, Paris, France.
Wafa FriguiInstitut Pasteur, Université Paris Cité, CNRS UMR 6047, Unit for Integrated Mycobacterial Pathogenomics, Paris, France.
Camille KeckInstitut Pasteur, Université Paris Cité, CNRS UMR 6047, Unit for Integrated Mycobacterial Pathogenomics, Paris, France.
Claude GutierrezInstitut de Pharmacologie et de Biologie Structurale, IPBS, Université de Toulouse, CNRS, UPS, Toulouse, France.
Olivier NeyrollesInstitut de Pharmacologie et de Biologie Structurale, IPBS, Université de Toulouse, CNRS, UPS, Toulouse, France.
Nathalie AulnerInstitut Pasteur, Université Paris Cité, UTechS BioImaging-C2RT, Paris, France.
Antonello MaiDepartment of Drug Chemistry and Technologies, Sapienza University of Rome, Rome, Italy.
Mélanie HamonInstitut Pasteur, Université Paris Cité, Chromatine et Infection unit, Paris, France.
Luis B BarreiroDepartment of Genetic Medicine, University of Chicago, Chicago, Illinois, United States of America.
Priscille BrodinUniversité de Lille, CNRS, INSERM, CHU Lille, Institut Pasteur de Lille, U1019 - UMR 9017 - CIIL - Center for Infection and Immunity of Lille, Lille, France.
Roland BroschInstitut Pasteur, Université Paris Cité, CNRS UMR 6047, Unit for Integrated Mycobacterial Pathogenomics, Paris, France.
Dante RotiliDepartment of Drug Chemistry and Technologies, Sapienza University of Rome, Rome, Italy.
Ludovic TailleuxInstitut Pasteur, Université Paris Cité, CNRS UMR 6047, Unit for Integrated Mycobacterial Pathogenomics, Paris, France.ORCID 0000-0003-3931-1052

Funding

French National Research AgencyInstitut Pasteur
6 · The paper itself

Abstract

Antituberculosis drugs, mostly developed over 60 years ago, combined with a poorly effective vaccine, have failed to eradicate tuberculosis. More worryingly, multiresistant strains of Mycobacterium tuberculosis (MTB) are constantly emerging. Innovative strategies are thus urgently needed to improve tuberculosis treatment. Recently, host-directed therapy has emerged as a promising strategy to be used in adjunct with existing or future antibiotics, by improving innate immunity or limiting immunopathology. Here, using high-content imaging, we identified novel 1,2,4-oxadiazole-based compounds, which allow human macrophages to control MTB replication. Genome-wide gene expression analysis revealed that these molecules induced zinc remobilization inside cells, resulting in bacterial zinc intoxication. More importantly, we also demonstrated that, upon treatment with these novel compounds, MTB became even more sensitive to antituberculosis drugs, in vitro and in vivo, in a mouse model of tuberculosis. Manipulation of heavy metal homeostasis holds thus great promise to be exploited to develop host-directed therapeutic interventions.

Indexed as

Antitubercular AgentsDisease Models, AnimalMacrophagesMycobacterium tuberculosisOxadiazolesTuberculosisZincAnimalsDrug SynergismFemaleHumansMiceMice, Inbred C57BLAntitubercular AgentsOxadiazolesZinc

Identifiers

PMID38683873
PMCPMC11081512

What OpenQuestion holds

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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.