Abstract
Antibiotic-resistant bacterial infections cause 1.27 million deaths annually, with forecasts suggesting up to 40 million mortalities by 2050 (Centers for Disease Control and Prevention, 2025; Naddaf, 2024). Pseudomonas aeruginosa is a “Priority 1” critical pathogen in this crisis, often forming biofilms encased in extracellular polymeric substances (EPS) that promote high antibiotic resistance and virulence through quorum sensing. While bacteriophages offer an orthogonal treatment, their narrow host range limits clinical utility. The significance of this project lies in overcoming these restrictions through the precision engineering of viral attachment proteins to target specific resistant strains. The broad objective is to expand the T7 lytic phage host range by redesigning its tail fibers to target P. aeruginosa. In the initial adsorption stage, phages use receptor-binding proteins (RBPs) on their tail fibers to bind to cell wall components, eventually leading to bacterial lysis via holin and endolysin production.