The organization and evolution of receptor binding proteins in Klebsiella phages by exploiting novel tools in synthetic biology

The most intense co-evolution process on our globe takes place between bacteria and bacteriophages. Every phage infection is initiated by the recognition of a specific receptor located on the bacterial cell surface by the phage’s receptor binding protein (RBP). I have elaborated before the modular build-up of Klebsiella phage RBPs. I found that N-terminal structural domains needed to organize the attachment of RBP systems to the phage particle are recycled among many phages. On the contrary, the C-terminal specificity domains are highly diverse and subject to intense horizontal exchanges for a rapid adaptation to specific hosts. Our recent discovery of carbohydrate binding modules in a RBP will allow me to unravel their role in the observed high receptor specificity, and accordingly their influence on the phage host spectrum. I have also unraveled a system to branch RBPs to build up a complex of multiple RBPs. Therefore, I will further elucidate RBP-RBP interactions to better understand this hierarchical assembly mechanism of multiple RBPs in a single phage. Based on a good knowledge of the modular RBP organization in Klebsiella phages, I will study natural horizontal transfer events between non-related phages and mimic this natural process by a blend of protein engineering and synthetic biology techniques. Phages with a programmed host specificity can eventually become an alternative method to fight multidrug-resistant bacteria.