I Atanaskovic - Import mechanism of Pyocin G, folded protein antibiotic active against P. aeruginosa

Pseudomonas aeruginosa is a priority pathogen for the development of new
antibiotics, especially because multidrug-resistant strains of this bacterium cause severe nosocomial infections and are the main cause of death in cystic fibrosis patients. Pyocins, the bacteriocins of P. aeruginosa, are potent and versatile protein antibiotics used in bacterial competition. Pyocins are produced by more than 90% of P. aeruginosa strains and can be used as a last resort against this bacterium. In this talk, I will present my data on the killing mechanism of a newly discovered pyocin called Pyocin G (PyoG). PyoG recognises bacterial cells by binding to Hur, a TonB-dependent transporter for the outer membrane. Both pyocin and Hur interact with TonB1, which in complex with ExbB-ExbD links the proton motive force generated by the inner membrane to the energy-dependent translocation of
pyocin across the outer membrane. The translocation of PyoG across the inner membrane depends on the conserved AAA+ ATPase/protease FtsH, which is located in the inner membrane. This research opens up new perspectives for the transport of folded proteins across the bacterial cell envelope, which has important implications for the development of antimicrobials.