Zobrazit v EDS

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

Uloženo v:
Podrobná bibliografie
Název: Uncovering nitroxoline activity spectrum, mode of action and resistance across Gram-negative bacteria.
Autoři: Cacace, Elisabetta, Tietgen, Manuela, Steinhauer, Meike, Mateus, André, Schultze, Tilman G., Eckermann, Marina, Galardini, Marco, Varik, Vallo, Koumoutsi, Alexandra, Parzeller, Jordan J., Corona, Federico, Orakov, Askarbek, Knopp, Michael, Brauer-Nikonow, Amber, Bork, Peer, Romao, Celia V., Zimmermann, Michael, Cloetens, Peter, Savitski, Mikhail M., Typas, Athanasios
Zdroj: Nature Communications; 4/22/2025, Vol. 16 Issue 1, p1-16, 16p
Témata: LIFE sciences, URINARY tract infections, GRAM-negative bacteria, BACTERIAL cells, BACTERIAL physiology, COPPER
Abstrakt: 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. Nitroxoline is a bacteriostatic quinoline antibiotic, known to form complexes with metals, with few clinical applications. Here, Cacace et al. show that the compound displays a broad activity spectrum, with species-specific bactericidal activity, and acts as a metallophore inducing copper and zinc intoxication in bacterial cells. [ABSTRACT FROM AUTHOR]
Copyright of Nature Communications is the property of Springer Nature and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
Databáze: Complementary Index
Popis
Abstrakt: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. Nitroxoline is a bacteriostatic quinoline antibiotic, known to form complexes with metals, with few clinical applications. Here, Cacace et al. show that the compound displays a broad activity spectrum, with species-specific bactericidal activity, and acts as a metallophore inducing copper and zinc intoxication in bacterial cells. [ABSTRACT FROM AUTHOR]
ISSN:20411723
DOI:10.1038/s41467-025-58730-5