The global rise of antibiotic resistance poses a severe healthcare challenge, necessitating alternative approaches to combat bacterial infections. Bacteriophages, or phages, have emerged as a promising alternative to traditional antibiotics, given their specificity and ability to evolve alongside bacterial targets. However, despite a decade of progress and clinical trials, traditional phage therapy faces significant challenges, especially due to the high specificity of phages, which limits their effectiveness against diverse bacterial strains.My research aims to address this limitation by developing a platform approach using filamentous M13 phages as a versatile scaffold to target a broad spectrum of gram-negative bacteria. Building on previous work in our lab, we employed two complementary strategies: First, we constructed a phage bank, a diverse library of engineered phages specific to gram-negative bacteria. This allows for the rapid isolation of phages capable of binding to specific bacterial isolates. Second, we developed a single engineered phage with broad binding capability across multiple bacterial strains, maximizing its versatility as a therapeutic agent. These two strategies form the foundation of two research papers demonstrating the feasibility and unique advantages of each approach. We then advanced our work by conjugating these selected phages with last-line antibiotics, transforming them into targeted drug delivery vehicles—what we term phage-drug conjugates (PDCs). This strategy significantly enhances the therapeutic index of last-line antibiotics by concentrating drug delivery directly at infection sites, thereby increasing efficacy by one to two orders of magnitude in both in vitro and in vivo models. Our resulting drug candidates not only show improved efficacy but also exhibit a favorable safety profile and clinically relevant biodistribution. This PDC platform technology opens new avenues for treating antibiotic-resistant infections and highlights the potential of phages as a foundation for a versatile, targeted drug delivery system.