Genomic surveillance as a scalable framework for precision phage therapy against antibiotic-resistant pathogens
Mihály Koncz, Tamás Stirling, Hiba Hadj Mehdi, Orsolya Méhi, Bálint Eszenyi, András Asbóth, Gábor Apjok, Ákos Tóth, László Orosz, Bálint Márk Vásárhelyi, Eszter Ari, Lejla Daruka, Tamás F. Polgár, György Schneider, Sif Aldin Zalokh, Mónika Számel, Gergely Fekete, Balázs Bohár, Karolina Nagy Varga, Ádám Visnyovszki, Edit Székely, Monica Licker, Oana Izmendi, Carmen Costache, Ina Gajić, Bojana Luković, Szabolcs Molnár, Uzonka Orsolya Szőcs-Gazdi, Csilla Bozai, Marina Indreas, Katalin Kristóf, Charles Van der Henst, Anke Breine, Csaba Pál, Balázs Papp, Bálint Kintses
Abstract
Phage therapy is gaining increasing interest in the fight against critically antibiotic-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 phylogeographic analysis with high-throughput phage typing to guide the development of precision phage cocktails targeting carbapenem-resistant Acinetobacter 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 6 years. As we demonstrate in Eastern Europe, this spatiotemporal distribution enables preemptive preparation of region-specific phage collections that target most local infections. Finally, we showcase the efficacy of phage cocktails against prevalent strain types using in vitro and animal infection models. Ultimately, genomic surveillance identifies patients benefiting from the same phages across geographical scales, thus providing a scalable framework for precision phage therapy.