摘要：SummaryPseudomonas aeruginosainfections can be difficult to treat and new therapeutics are needed. Bacteriophage therapy is a promising alternative to traditional antibiotics, but large numbers of isolated and characterized phages are lacking. We collected 23 diverseP.aeruginosaisolates from people with cystic fibrosis (CF) and clinical infections, and used them to screen and isolate over a dozenP.aeruginosa-targeting phages from hospital wastewater. Phages were characterized with genome sequencing, comparative genomics, and lytic activity screening against all 23 bacterial host isolates. We evolved bacterial mutants that were resistant to phage infection for four different phages, and used genome sequencing and functional analysis to study them further. We also tested phages for their ability to killP.aeruginosagrown in biofilmsin vitroandex vivoon CF airway epithelial cells. Overall, this study demonstrates how systematic genomic and phenotypic characterization can be deployed to develop bacteriophages as precision antibiotics.Graphical abstractDisplay OmittedHighlights•P.aeruginosa-targeting bacteriophages reflect the diversity of their hosts•Phage resistance drives evolutionary trade-offs in virulence and drug resistance•Phages can kill bacteria grow in biofilmsin vitroandex vivoMicrobiology; Virology
