Reprogramming Bacteriophage Host Range through Structure-Guided Design of Chimeric Receptor Binding Proteins

摘要: Bacteriophages provide excellent tools for diagnostics, remediation, and targeted microbiome manipulation, yet isolating viruses with suitable host specificity remains challenging. Using Listeria phage PSA, we present a synthetic biology blueprint host-range engineering through modification of serovar-specific receptor binding proteins (RBPs). We identify Gp15 as the PSA RBP construct library featuring sequence-randomized RBPs, from which range mutants are isolated subsequently integrated into synthetic, polyvalent extended range. To enable rational design chimeric determine crystal structure receptor-binding carboxyl terminus at 1.7-A resolution employ bioinformatics to compatible, prophage-encoded RBPs targeting different serovars. Structure-guided enables exchange heterologous head, neck, or shoulder domains generate phages predictable ranges. These strategies will facilitate development biologics based on standardized virus scaffolds tunable specificities.