Genomic surveillance as a scalable framework for precision phage therapy against antibiotic-resistant pathogens
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.
Authors
- Eszter Ari (ORCID: https://orcid.org/0000-0001-7774-1067)
- Mihály Koncz (ORCID: https://orcid.org/0009-0007-0166-0755)
- Orsolya Méhi (ORCID: https://orcid.org/0009-0004-7918-913X)
- Edit Székely (ORCID: https://orcid.org/0000-0002-3350-1675)
- Balázs Bohár (ORCID: https://orcid.org/0000-0002-3033-5448)
- Monica Licker (ORCID: https://orcid.org/0000-0002-9245-5883)
- Gergely Fekete (ORCID: https://orcid.org/0000-0001-9939-4860)
- Mónika Számel
- Karolina Nagy Varga
- Ádám Visnyovszki (ORCID: https://orcid.org/0000-0001-6825-1496)
- Balázs Papp (ORCID: https://orcid.org/0000-0003-3093-8852)
- Bojana Luković (ORCID: https://orcid.org/0000-0003-2830-2572)
- Gábor Apjok (ORCID: https://orcid.org/0000-0002-8627-2378)
- Lejla Daruka (ORCID: https://orcid.org/0000-0002-3462-0887)
- Ákos Tóth (ORCID: https://orcid.org/0000-0003-0048-567X)
- Bálint Kintses (ORCID: https://orcid.org/0000-0003-0844-0310)
- Ina Gajić (ORCID: https://orcid.org/0000-0002-1578-2776)
- Tamás F. Polgár (ORCID: https://orcid.org/0000-0002-6287-1093)
- Anke Breine (ORCID: https://orcid.org/0000-0003-2805-2980)
- György Schneider (ORCID: https://orcid.org/0000-0003-4424-7585)
- Charles Van der Henst (ORCID: https://orcid.org/0000-0002-3451-9439)
- Carmen Costache (ORCID: https://orcid.org/0000-0003-2640-0072)
- Csaba Pál (ORCID: https://orcid.org/0000-0002-5187-9903)
- Bálint Eszenyi
- László Orosz
- Marina Indreas
- Szabolcs Molnár
- András Asbóth
- Bálint Márk Vásárhelyi (ORCID: https://orcid.org/0000-0003-1782-8691)
- Tamás Stirling (ORCID: https://orcid.org/0000-0002-8964-6443)
- Oana Izmendi (ORCID: https://orcid.org/0000-0001-7644-8109)
- Sif Aldin Zalokh
- Uzonka Orsolya Szőcs-Gazdi
- Csilla Bozai
- Hiba Hadj Mehdi (ORCID: https://orcid.org/0009-0009-2875-1686)
- Koloman Krištof (ORCID: https://orcid.org/0000-0003-1573-4667)
Institutions
- Semmelweis University (HU)
- Spiru Haret University (RO)
- UNESCO (FR)
- University of Szeged (HU)
- HUN-REN Szegedi Biológiai Kutatóközpont (HU)
- University of Belgrade (RS)
- Institute of Biochemistry (HU)
- National Public Health and Medical Officer Service (HU)
- Technosam (Romania) (RO)
- Academy of Engineering Sciences of Serbia (RS)
- County Hospital (GB)
- University of Bacău (RO)
- University of Pecs (HU)
Publication Details
- Journal
- Cell
- Published
- 2024-09-26
- DOI
- https://doi.org/10.1016/j.cell.2024.09.009
- Citations
- 39
- Primary Topic
- Bacteriophages and microbial interactions
- Type
- article
- Field-Weighted Citation Impact
- 17.90
Funders
- Nemzeti Kutatási Fejlesztési és Innovációs Hivatal