How the protein antibiotic pyocin S5 kills Pseudomonas aeruginosa (360G-Wellcome-109027_Z_15_A)

With the rise in multidrug resistance as a result of broad spectrum antibiotic use, bacteriocins have received attention as potential new antibiotics. Bacteriocins are bacterial toxins that kill closely related strains and species. Pyocin S5, a bacteriocin targeting Pseudomonas aeruginosa, a leading cause of multidrug resistant nosocomial infections, was shown to be effective against pneumonia in mice. Pyocin S5 depends on the iron receptor FptA and kills cells by depolarizing the inner membrane. Little else is known about its mode of action. Pyocin S5-producing cells harbour a gene encoding a small immunity protein, predicted to localize to the inner membrane, which protects from the action of this pyocin. In this PhD project, I aim to investigate the molecular mechanism of pyocin S5 binding to P. aeruginosa cells, its mechanism of translocation to the periplasm and the immunity protein’s mode of action. These aims will be approached using a combination of structural and biophysical methods as well as functional assays and a variety of fluorescence microscopy techniques.