{
    "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.",
    "authors": [
        {
            "affiliation": "Goethe University Frankfurt, University Hospital, Institute for Medical Microbiology and Infection Control, Frankfurt, Germany.\nEuropean Molecular Biology Laboratory, Genome Biology Unit, Heidelberg, Germany.",
            "firstname": "Elisabetta",
            "initials": "E",
            "lastname": "Cacace"
        },
        {
            "affiliation": "Goethe University Frankfurt, University Hospital, Institute for Medical Microbiology and Infection Control, Frankfurt, Germany.",
            "firstname": "Manuela",
            "initials": "M",
            "lastname": "Tietgen"
        },
        {
            "affiliation": "Goethe University Frankfurt, University Hospital, Institute for Medical Microbiology and Infection Control, Frankfurt, Germany.",
            "firstname": "Meike",
            "initials": "M",
            "lastname": "Steinhauer"
        },
        {
            "affiliation": "European Molecular Biology Laboratory, Genome Biology Unit, Heidelberg, Germany.",
            "firstname": "Andr\u00e9",
            "initials": "A",
            "lastname": "Mateus"
        },
        {
            "affiliation": "Goethe University Frankfurt, University Hospital, Institute for Medical Microbiology and Infection Control, Frankfurt, Germany.",
            "firstname": "Tilman G",
            "initials": "TG",
            "lastname": "Schultze"
        },
        {
            "affiliation": "European Synchrotron Radiation Facility (ESRF), Grenoble, France.\nInstitute of Applied Physics, University of Bern, Bern, Switzerland.",
            "firstname": "Marina",
            "initials": "M",
            "lastname": "Eckermann"
        },
        {
            "affiliation": "Institute 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.\nCluster of Excellence RESIST (EXC 2155), Hannover Medical School (MHH), Hannover, Germany.",
            "firstname": "Marco",
            "initials": "M",
            "lastname": "Galardini"
        },
        {
            "affiliation": "European Molecular Biology Laboratory, Genome Biology Unit, Heidelberg, Germany.",
            "firstname": "Vallo",
            "initials": "V",
            "lastname": "Varik"
        },
        {
            "affiliation": "European Molecular Biology Laboratory, Genome Biology Unit, Heidelberg, Germany.",
            "firstname": "Alexandra",
            "initials": "A",
            "lastname": "Koumoutsi"
        },
        {
            "affiliation": "Goethe University Frankfurt, University Hospital, Institute for Medical Microbiology and Infection Control, Frankfurt, Germany.",
            "firstname": "Jordan J",
            "initials": "JJ",
            "lastname": "Parzeller"
        },
        {
            "affiliation": "European Molecular Biology Laboratory, Genome Biology Unit, Heidelberg, Germany.",
            "firstname": "Federico",
            "initials": "F",
            "lastname": "Corona"
        },
        {
            "affiliation": "European Molecular Biology Laboratory, Structural and Computational Biology Unit, Heidelberg, Germany.",
            "firstname": "Askarbek",
            "initials": "A",
            "lastname": "Orakov"
        },
        {
            "affiliation": "European Molecular Biology Laboratory, Genome Biology Unit, Heidelberg, Germany.",
            "firstname": "Michael",
            "initials": "M",
            "lastname": "Knopp"
        },
        {
            "affiliation": "European Molecular Biology Laboratory, Structural and Computational Biology Unit, Heidelberg, Germany.",
            "firstname": "Amber",
            "initials": "A",
            "lastname": "Brauer-Nikonow"
        },
        {
            "affiliation": "European Molecular Biology Laboratory, Structural and Computational Biology Unit, Heidelberg, Germany.",
            "firstname": "Peer",
            "initials": "P",
            "lastname": "Bork"
        },
        {
            "affiliation": "Instituto de Tecnologia Qu\u00edmica e Biol\u00f3gica Ant\u00f3nio Xavier, Universidade Nova de Lisboa, Oeiras, Portugal.",
            "firstname": "Celia V",
            "initials": "CV",
            "lastname": "Romao"
        },
        {
            "affiliation": "Cluster of Excellence RESIST (EXC 2155), Hannover Medical School (MHH), Hannover, Germany.",
            "firstname": "Michael",
            "initials": "M",
            "lastname": "Zimmermann"
        },
        {
            "affiliation": "European Synchrotron Radiation Facility (ESRF), Grenoble, France.",
            "firstname": "Peter",
            "initials": "P",
            "lastname": "Cloetens"
        },
        {
            "affiliation": "European Molecular Biology Laboratory, Genome Biology Unit, Heidelberg, Germany.",
            "firstname": "Mikhail M",
            "initials": "MM",
            "lastname": "Savitski"
        },
        {
            "affiliation": "European Molecular Biology Laboratory, Genome Biology Unit, Heidelberg, Germany.",
            "firstname": "Athanasios",
            "initials": "A",
            "lastname": "Typas"
        },
        {
            "affiliation": "Goethe University Frankfurt, University Hospital, Institute for Medical Microbiology and Infection Control, Frankfurt, Germany. goettig@med.uni-frankfurt.de.",
            "firstname": "Stephan",
            "initials": "S",
            "lastname": "G\u00f6ttig"
        }
    ],
    "conclusions": null,
    "copyrights": "\u00a9 2025. The Author(s).",
    "doi": "10.1038/s41467-025-58730-5",
    "journal": "Nature communications",
    "keywords": [],
    "methods": null,
    "publication_date": "2025-04-23",
    "pubmed_id": "40263263\n25427651\n29271346\n36009974\n3302880\n29539622\n35721137\n34245904\n29214226\n32750466\n34163027\n30377287\n26447757\n30241558\n33046984\n31464130\n35907036\n30184207\n27596848\n7793877\n22926564\n28110918\n32364820\n34865870\n4854024\n810137\n25182654\n31633764\n38063385\n22563326\n30792131\n7968625\n34788072\n24217699\n17040922\n24867991\n30875778\n28652855\n32133759\n33299184\n21185072\n16738554\n15851036\n27161117\n1406489\n20442333\n38085067\n24205499\n11136469\n35194207\n23170953\n28598435\n19416816\n20233928\n31586033\n30824435\n12563288\n25266384\n32845936\n34929542\n9171423\n32576675\n24325250\n2848006\n28504927\n15673787\n21377839\n25074541\n28938624\n12591940\n29114953\n28284195\n38839776\n31292653\n16354747\n34520557\n26921390\n25756107\n30464214\n26379230\n33188197\n37770760\n10735988\n28211844\n16859555\n25605792\n24642063\n28383659\n31091262\n37156916\n33956157\n10592235\n20937596\n15987659\n32698896\n28460117\n19304878",
    "results": null,
    "title": "Uncovering nitroxoline activity spectrum, mode of action and resistance across Gram-negative bacteria.",
    "xml": "<Element 'PubmedArticle' at 0x7885038cfb50>"
}