The Urinary Antibiotic 5-Nitro-8-Hydroxyquinoline (Nitroxoline) Reduces the Formation and Induces the Dispersal of Pseudomonas aeruginosa Biofilms by Chelation of Iron and Zinc

Since cations have been reported as essential regulators of biofilm, we investigated the potential of the broad-spectrum antimi-crobial and cation-chelator nitroxoline as an antibiofilm agent. Biofilmmass synthesis was reduced by up to 80 % at sub-MIC nitroxoline concentrations in Pseudomonas aeruginosa, and structures formed were reticulate rather than compact. In pre-formed biofilms, viable cell counts were reduced by 4 logs at therapeutic concentrations. Complexation of iron and zinc was demonstrated to underlie nitroxoline’s potent antibiofilm activity. Biofilm formation on epithelia and foreign devices poses a se-vere clinical challenge, as bacteria embedded in these struc-tures are protected from antimicrobial therapy and host immune responses (6, 8, 13).Maintenance of these complex bacterial com-munities is a dynamic process that has previously been shown to be regulated by various divalent cations, including Fe2, Zn2, Mg2, and Ca2 (3, 5, 21, 22). Currently, attempts are under way to identify therapeutically applicable compounds that would show strong chelating properties without concomitant immuno-genicity or toxicity (1, 18, 19). The antimicrobial effects of the urinary antibiotic nitroxoline have long been known to depend o