Genomic surveillance as a scalable framework for precision phage therapy against antibiotic-resistant pathogens

Koncz, Mihály and Stirling, Tamás and Hadj Mehdi, Hiba and Méhi, Orsolya Katinka and Eszenyi, Bálint Dénes and Asbóth, András and Apjok, Gábor and Tóth, Ákos and Orosz, László and Vásárhelyi, Bálint Márk and Ari, Eszter and Daruka, Lejla and Polgár, Tamás Ferenc and Schneider, György and Zalokh, Sif Aldin and Számel, Mónika and Fekete, Gergely and Bohár, Balázs and Nagy Varga, Karolina and Visnyovszki, Ádám and Székely, Edit and Licker, Monica-Sorina and Izmendi, Oana and Costache, Carmen and Gajic, Ina and Lukovic, Bojana and Molnár, Szabolcs and Szőcs-Gazdi, Uzonka Orsolya and Bozai, Csilla and Indreas, Marina and Pál, Csaba and Papp, Balázs and Kintses, Bálint (2024) Genomic surveillance as a scalable framework for precision phage therapy against antibiotic-resistant pathogens. CELL, 187. pp. 1-18. ISSN 0092-8674 (In Press)

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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.

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