匈牙利国立生物技术实验室Bálint Kintses等研究人员发现，基因组监测可作为一种可扩展框架，用于靶向抗生素耐药病原体的精准噬菌体治疗。相关论文于2024年9月26日在线发表在《细胞》杂志上。

研究人员结合大规模的系统地理分析和高通量噬菌体分型，以指导针对耐卡巴平类药物的铜绿假单胞菌（Acinetobacter baumannii）的精准噬菌体鸡尾酒的开发，这是一种优先考虑的病原体。分析显示，少数菌株类型主导了各个世界地区的感染，其地理分布在6年内保持稳定。

正如研究人员在东欧所示，这种时空分布使得能够提前准备针对大多数地方感染的区域特定噬菌体库。最后，研究人员展示了使用体外和动物感染模型，噬菌体鸡尾酒对流行菌株类型的有效性。

因此，基因组监测识别出在不同地理范围内受益于相同噬菌体的患者，从而提供了一种可扩展的精准噬菌体治疗框架。

研究人员表示，噬菌体治疗在对抗严重抗生素耐药医院病原体的斗争中受到越来越多的关注。然而，噬菌体狭窄的宿主范围限制了广泛有效的噬菌体治疗的发展，并要求精准的方法。

附：英文原文

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

Author: 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 Ferenc Polgár, Gyrgy Schneider, Sif Aldin Zalokh, Mónika Számel, Gergely Fekete, Balázs Bohár, Karolina Nagy Varga, ádám Visnyovszki, Edit Székely, Monica-Sorina Licker, Oana Izmendi, Carmen Costache, Ina Gajic, Bojana Lukovic, Szabolcs Molnár, Uzonka Orsolya Szcs-Gazdi, Csilla Bozai, Marina Indreas, Katalin Kristóf, Charles Van der Henst, Anke Breine, Csaba Pál, Balázs Papp, Bálint Kintses

Issue&Volume: 2024-09-26

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.

DOI: 10.1016/j.cell.2024.09.009

Source: https://www.cell.com/cell/abstract/S0092-8674(24)01027-4