Antimicrobial activity of iron-depriving pyoverdines against human opportunistic pathogens

Abstract

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 environmental <i>Pseudomonas</i> spp., have strong antibacterial properties by inducing iron starvation and growth arrest in pathogens. A screen of 320 natural <i>Pseudomonas</i> isolates 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 pathogens <i>Acinetobacter baumannii</i>, <i>Klebsiella pneumoniae,</i> and <i>Staphylococcus aureus</i> in a concentration- and iron-dependent manner. Pyoverdine increased survival of infected <i>Galleria mellonella</i> host larvae and showed low toxicity for the host, mammalian cell lines, and erythrocytes. Furthermore, experimental evolution of pathogens combined with whole-genome sequencing revealed limited 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.