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

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

SUBMITTER: Cacace E 

PROVIDER: S-EPMC12015411 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature