Synthetic and Systems Biology Unit, Institute of Biochemistry, National Laboratory of Biotechnology, HUN-REN Biological Research Centre, Temesvári Krt. 62, 6726 Szeged, Hungary; HCEMM-BRC Translational Microbiology Research Group, Budapesti út 9, 6728 Szeged, Hungary.
Synthetic and Systems Biology Unit, Institute of Biochemistry, National Laboratory of Biotechnology, HUN-REN Biological Research Centre, Temesvári Krt. 62, 6726 Szeged, Hungary; HCEMM-BRC Translational Microbiology Research Group, Budapesti út 9, 6728 Szeged, Hungary; Doctoral School of Biology, University of Szeged, Dugonics tér 13, 6720 Szeged, Hungary.
Cell. 2024 Oct 17;187(21):5901-5918.e28. doi: 10.1016/j.cell.2024.09.009. Epub 2024 Sep 26.
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.
噬菌体疗法在对抗严重抗生素耐药性医院病原体的斗争中越来越受到关注。然而,噬菌体的宿主范围狭窄限制了广泛有效的噬菌体治疗药物的发展,并需要精确的方法。在这里,我们将大规模系统地理学分析与高通量噬菌体分型相结合,指导开发针对碳青霉烯类耐药鲍曼不动杆菌的精准噬菌体鸡尾酒,这种细菌是一种首要的病原体。我们的分析表明,在每个世界区域,少数菌株类型主导着感染,并且它们在 6 年内的地理分布保持稳定。正如我们在东欧所展示的那样,这种时空分布使得能够预先准备针对大多数本地感染的特定区域的噬菌体集合。最后,我们使用体外和动物感染模型展示了噬菌体鸡尾酒对流行菌株类型的疗效。最终,基因组监测确定了在地理尺度上受益于相同噬菌体的患者,从而为精准噬菌体治疗提供了一个可扩展的框架。
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