Optimized preparation pipeline for emergency phage therapy against Pseudomonas aeruginosa at Yale University
Silvia Würstle, Alina Lee, Kaitlyn E. Kortright, Franziska Winzig, William An, Gail Stanley, Govindarajan Rajagopalan, Z. Harris, Ying Sun, Buqu Hu, Michael Blazanin, Maryam Hajfathalian, Paul L. Bollyky, Paul E. Turner, Jonathan L. Koff, Benjamin K. Chan
Abstract
Bacteriophage therapy is one potential strategy to treat antimicrobial resistant or persistent bacterial infections, and the year 2021 marked the centennial of Felix d'Hérelle's first publication on the clinical applications of phages. At the Center for Phage Biology & Therapy at Yale University, a preparatory modular approach has been established to offer safe and potent phages for single-patient investigational new drug applications while recognizing the time constraints imposed by infection(s). This study provides a practical walkthrough of the pipeline with an Autographiviridae phage targeting Pseudomonas aeruginosa (phage vB_PaeA_SB, abbreviated to ΦSB). Notably, a thorough phage characterization and the evolutionary selection pressure exerted on bacteria by phages, analogous to antibiotics, are incorporated into the pipeline.