Pathogen genomic surveillance as a scalable framework for precision phage therapy

Abstract

AbstractPhage therapy is gaining increasing interest in the fight against critically resistant nosocomial pathogens. However, the narrow host range of bacteriophages hampers the development of broadly effective phage therapeutics and demands precision approaches. Here we combine large-scale phylogeographical analysis with high-throughput phage typing to guide the development of precision phage cocktails targeting carbapenem-resistantAcinetobacter baumannii,a top-priority pathogen. Our analysis reveals that a few strain types dominate infections in each world region, with their geographical distribution remaining stable within six years. As we demonstrate in Eastern Europe, this spatio-temporal distribution enables preemptive preparation of region-specific phage collections that target most local infections. Finally, we showcase the efficacy of a four-phage cocktail against the most prevalent strain type in bothin vitroandin vivoanimal infection models. Ultimately, genomic surveillance identifies patients benefiting from the same phages across geographical scales, thus providing a scalable framework for precision phage therapy.HighlightsA few carbapenem-resistantAcinetobacter baumanniitypes dominate infections worldwidePhylogeography reveals stable strain composition of individual countries over a six-year periodThis spatio-temporal distribution allows preemptive preparation of region-specific phage collectionsA four-phage cocktail is efficacious against the most prevalent strain type in Europe.