Antimicrobial activity of iron-depriving pyoverdines against human opportunistic pathogens

The global rise of antibiotic resistance calls for new drugs against bacterial pathogens. A common approach is to search for natural compounds deployed by microbes to inhibit competitors. Here we show that the iron chelating pyoverdines, siderophores produced by environmentalPseudomonasspp., have strong antibacterial properties by inducing iron starvation and growth arrest in pathogens. A screen of 320 naturalPseudomonasisolates used against 12 human pathogens uncovered several pyoverdines with particularly high antibacterial properties and distinct chemical characteristics. The most potent pyoverdine effectively reduced growth of the pathogensAcinetobacter baumannii,Klebsiella pneumoniaeandStaphylococcus aureusin a concentration- and iron-dependent manner. Pyoverdine increased survival of infectedGalleria mellonellahost larvae, and showed low toxicity for the host, mammalian cell lines, and erythrocytes. Furthermore, experimental evolution combined with whole-genome sequencing revealed reduced potentials for resistance evolution compared to an antibiotic. Thus, pyoverdines from environmental strains have the potential to become a new class of sustainable antibacterials against specific human pathogens.