Evidence map›Paper›PMID 40263263›Full record

ArticleNature communications2025

Uncovering nitroxoline activity spectrum, mode of action and resistance across Gram-negative bacteria.

Elisabetta Cacace, Manuela Tietgen, Meike Steinhauer, André Mateus, Tilman G Schultze, Marina Eckermann, Marco Galardini, Vallo Varik, Alexandra Koumoutsi, Jordan J Parzeller and 11 more

Abstract read
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing 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

9 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Article
  6. Nitroxoline exerts potent anti-Antimicrobial agents and chemotherapy · 2026
    Article
  7. Article
  8. Article
  9. 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.

Elisabetta CacaceGoethe University Frankfurt, University Hospital, Institute for Medical Microbiology and Infection Control, Frankfurt, Germany.ORCID http://orcid.org/0000-0001-8239-0353
Manuela TietgenGoethe University Frankfurt, University Hospital, Institute for Medical Microbiology and Infection Control, Frankfurt, Germany.
Meike SteinhauerGoethe University Frankfurt, University Hospital, Institute for Medical Microbiology and Infection Control, Frankfurt, Germany.
André MateusEuropean Molecular Biology Laboratory, Genome Biology Unit, Heidelberg, Germany.
Tilman G SchultzeGoethe University Frankfurt, University Hospital, Institute for Medical Microbiology and Infection Control, Frankfurt, Germany.
Marina EckermannEuropean Synchrotron Radiation Facility (ESRF), Grenoble, France.
Marco GalardiniInstitute for Molecular Bacteriology, TWINCORE Centre for Experimental and Clinical Infection Research, a joint venture between the Hannover Medical School (MHH) and the Helmholtz Centre for Infection Research (HZI), Hannover, Germany.ORCID http://orcid.org/0000-0003-2018-8242
Vallo VarikEuropean Molecular Biology Laboratory, Genome Biology Unit, Heidelberg, Germany.ORCID http://orcid.org/0000-0001-6900-6986
Alexandra KoumoutsiEuropean Molecular Biology Laboratory, Genome Biology Unit, Heidelberg, Germany.
Jordan J ParzellerGoethe University Frankfurt, University Hospital, Institute for Medical Microbiology and Infection Control, Frankfurt, Germany.
Federico CoronaEuropean Molecular Biology Laboratory, Genome Biology Unit, Heidelberg, Germany.
Askarbek OrakovEuropean Molecular Biology Laboratory, Structural and Computational Biology Unit, Heidelberg, Germany.ORCID http://orcid.org/0000-0001-6823-5269
Michael KnoppEuropean Molecular Biology Laboratory, Genome Biology Unit, Heidelberg, Germany.
Amber Brauer-NikonowEuropean Molecular Biology Laboratory, Structural and Computational Biology Unit, Heidelberg, Germany.ORCID http://orcid.org/0000-0003-4146-2458
Peer BorkEuropean Molecular Biology Laboratory, Structural and Computational Biology Unit, Heidelberg, Germany.
Celia V RomaoInstituto de Tecnologia Química e Biológica António Xavier, Universidade Nova de Lisboa, Oeiras, Portugal.ORCID http://orcid.org/0000-0002-9474-2405
Michael ZimmermannCluster of Excellence RESIST (EXC 2155), Hannover Medical School (MHH), Hannover, Germany.ORCID http://orcid.org/0000-0002-5797-3589
Peter CloetensEuropean Synchrotron Radiation Facility (ESRF), Grenoble, France.
Mikhail M SavitskiEuropean Molecular Biology Laboratory, Genome Biology Unit, Heidelberg, Germany.ORCID http://orcid.org/0000-0003-2011-9247
Athanasios TypasEuropean Molecular Biology Laboratory, Genome Biology Unit, Heidelberg, Germany.ORCID http://orcid.org/0000-0002-0797-9018
Stephan GöttigGoethe University Frankfurt, University Hospital, Institute for Medical Microbiology and Infection Control, Frankfurt, Germany. goettig@med.uni-frankfurt.de.ORCID http://orcid.org/0000-0001-6896-5309

Funding

Bundesministerium für Bildung und Forschung (Federal Ministry of Education and Research) LAMarCK, 031L0181ADeutsche Forschungsgemeinschaft (German Research Foundation) 390874280Vetenskapsrådet (Swedish Research Council) 2019-00666
6 · The paper itself

Abstract

Nitroxoline is a bacteriostatic quinoline antibiotic, known to form complexes with metals. Its clinical indications are limited to uncomplicated urinary tract infections, with a susceptibility breakpoint only available for Escherichia coli. Here, we test > 1000 clinical isolates and demonstrate a much broader activity spectrum and species-specific bactericidal activity, including Gram-negative bacteria for which therapeutic options are limited due to multidrug resistance. By combining genetic and proteomic approaches with direct measurement of intracellular metals, we show that nitroxoline acts as a metallophore, inducing copper and zinc intoxication in bacterial cells. The compound displays additional effects on bacterial physiology, including alteration of outer membrane integrity, which underpins nitroxoline's synergies with large-scaffold antibiotics and resensitization of colistin-resistant Enterobacteriaceae in vitro and in vivo. Furthermore, we identify conserved resistance mechanisms across bacterial species, often leading to nitroxoline efflux.

Indexed as

Anti-Bacterial AgentsGram-Negative BacteriaNitroquinolinesAnimalsColistinCopperDrug Resistance, BacterialDrug Resistance, Multiple, BacterialEscherichia coliHumansMicrobial Sensitivity TestsUrinary Tract InfectionsZincAnti-Bacterial AgentsColistinCopperNitroquinolinesnitroxolineZinc

Identifiers

PMID40263263
PMCPMC12015411

What Socratic 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 Socratic graph.