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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.
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1 Yale University, Yale Center for Phage Biology and Therapy, New Haven, USA (GRID:grid.47100.32) (ISNI:0000 0004 1936 8710); Yale University, Department of Ecology and Evolutionary Biology, New Haven, USA (GRID:grid.47100.32) (ISNI:0000 0004 1936 8710); Yale School of Medicine, Department of Internal Medicine, Section of Pulmonary, Critical Care, and Sleep Medicine, New Haven, USA (GRID:grid.47100.32) (ISNI:0000000419368710); Technical University of Munich, Munich, Germany (GRID:grid.6936.a) (ISNI:0000000123222966)
2 Yale University, Yale Center for Phage Biology and Therapy, New Haven, USA (GRID:grid.47100.32) (ISNI:0000 0004 1936 8710); Yale University, Department of Ecology and Evolutionary Biology, New Haven, USA (GRID:grid.47100.32) (ISNI:0000 0004 1936 8710)
3 Yale University, Department of Ecology and Evolutionary Biology, New Haven, USA (GRID:grid.47100.32) (ISNI:0000 0004 1936 8710); Technical University of Munich, Munich, Germany (GRID:grid.6936.a) (ISNI:0000000123222966)
4 Yale University, Department of Ecology and Evolutionary Biology, New Haven, USA (GRID:grid.47100.32) (ISNI:0000 0004 1936 8710)
5 Yale University, Yale Center for Phage Biology and Therapy, New Haven, USA (GRID:grid.47100.32) (ISNI:0000 0004 1936 8710); Yale School of Medicine, Department of Internal Medicine, Section of Pulmonary, Critical Care, and Sleep Medicine, New Haven, USA (GRID:grid.47100.32) (ISNI:0000000419368710)
6 Yale School of Medicine, Department of Internal Medicine, Section of Pulmonary, Critical Care, and Sleep Medicine, New Haven, USA (GRID:grid.47100.32) (ISNI:0000000419368710)
7 Stanford University, Division of Infectious Diseases and Geographic Medicine, Department of Medicine, Stanford, USA (GRID:grid.168010.e) (ISNI:0000 0004 1936 8956)
8 Yale University, Yale Center for Phage Biology and Therapy, New Haven, USA (GRID:grid.47100.32) (ISNI:0000 0004 1936 8710); Yale University, Department of Ecology and Evolutionary Biology, New Haven, USA (GRID:grid.47100.32) (ISNI:0000 0004 1936 8710); Yale School of Medicine, Department of Internal Medicine, Section of Pulmonary, Critical Care, and Sleep Medicine, New Haven, USA (GRID:grid.47100.32) (ISNI:0000000419368710); Yale School of Medicine, Program in Microbiology, New Haven, USA (GRID:grid.47100.32) (ISNI:0000000419368710)