PYANO · Retargeted Pyocins: A novel tool for combating major food borne pathogens and exploiting phage-host interactions

Retargeted Pyocins: A novel tool for combating major food borne pathogens and exploitingphage-host interactions

Campylobacter jejuni and Salmonella are the top-ranking foodborne pathogens of Europe. The economic burden resulting from these bacterial infections is substantial and has been estimated to exceed EUR 5.4 billion each year, due to loss in productivity, hospitalization, medicinal costs and management of associated chronic diseases. The problem is further accentuated by the increase in resistance to antibiotics commonly used in treatment of human C. jejuni and Salmonella infections. To tackle antimicrobial resistance development, the European Commission has emphasized an urgent need for developing new effective antimicrobials or alternatives for treatment. Natural predators of bacteria, bacteriophages, as well as phage-based therapeutics are promising alternatives to combat pathogenic bacteria. Being obligate parasites of the bacteria, phages bind to, infect and kill specific bacterial species, subspecies, serovars or even particular strains during their propagation. Their ability to recognize a bacterium is dependent on Receptor Binding Proteins (RBPs) found in the distal tip of phage tail structure. The RBP binds to a specific receptor on the bacterial surface thereby ensuring precision in host recognition. This astonishing specificity is a result of evolution and natural selection over millions of years which secures binding of the phage to a potential host. Due to the immense diversity of phages, RBPs present a rich source of biotechnological tools for specific targeting of any bacterial species with outstanding precision. PYANO aimed at discovering novel RBPs and to develop alternative phage-based therapeutics to control C. jejuni and Salmonella. PYANO combined these objectives by exploring R-type pyocins (hereafter referred as pyocins) as a novel, advanced and versatile approach. Pyocins are highly-ordered bacteriocins of pseudomonads that resembles a headless phage with a contractile tail. Like phages, these “nanoscale-injectors” bind to a bacterial receptor via tail fibers that determine the host specificity. Once specifically bound, the tail contracts and pyocins exert their highly potent bactericidal activity by punching a hole on the bacterial envelope that dissipates the membrane potential and kills the bacterial cell. Importantly, by fusing novel RBPs from different phages to the fibers of pyocins, the bactericidal activity of the chimeric pyocin can be directed towards bacteria that are recognized by the fused RBP. Therefore, successful binding of the novel RBP can be confirmed by clearance of the bacterial cells, which also allows high throughput screening of chimeric pyocins on an array of relevant bacterial strains. Moreover, chimeric pyocins are advantageous with regards to the phages as they circumvent the necessity of genome replication, and the immediate bactericidal activity from puncturing of the cell envelope prohibits development of bacterial resistance. These features consolidate chimeric pyocins as a powerful, cost-effective and phage-derived, green and biodegradable alternative to conventional antimicrobials.

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз