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.

Immune checkpoint blockade (ICB) has become a standard anti-cancer treatment, offering durable clinical benefits. However, the limited response rate of ICB necessitates biomarkers to predict and modulate the efficacy of the therapy. The gut microbiome's influence on ICB efficacy is of particular interest due to its modifiability through various interventions. However, gut microbiome biomarkers for ICB response have been inconsistent across different studies. Here, we identify TANB77, an uncultured and distinct bacterial clade, as the most consistent responder-enriched taxon through meta-analysis of ten independent ICB recipient cohorts. Traditional taxonomy fails to distinguish TANB77 from unrelated taxa, leading to its oversight. Mice with higher gut TANB77 abundance, either naturally or through transplantation, show improved response to anti-PD-1 therapy. Additionally, mice injected with TANB77-derived pilin-like protein exhibit improved anti-PD-1 therapy response, providing in vivo evidence for the beneficial role of the pilin-like protein. These findings suggest that pilins from the TANB77 order may enhance responses to ICB therapy across diverse cohorts of cancer patients.