Abstract：
Klebsiella pneumoniae, a major clinical pathogen known for causing severe infections, is attracting heightened attention due to its escalating antibiotic resistance. Phages are emerging as a promising alternative to antibiotics; however, their specificity to particular hosts often restricts their use. In this study, a collection of 114 phages is obtained and subjected to analysis against 238 clinical K. pneumoniae strains, revealing a spectrum of lytic behaviors. A correlation between putative tail protein clusters and lysis patterns leads to the discovery of six receptor-binding protein (RBP) clusters that determine host capsule tropism. Significantly, RBPs with cross-capsular lysis capabilities are identified. The newly-identified RBPs provide a toolbox for customizing phages to target diverse capsular types. Building on the toolbox, the engineered phages with altered RBPs successfully shifted and broadened their host capsule tropism, setting the stage for tunable phage that offer a precise and flexible solution to combat K. pneumoniae infections.
摘要：
肺炎克雷伯菌,一种以引起严重感染而闻名的主要临床病原体，由于其不断升级的抗生素耐药性，引起了越来越多的关注。噬菌体正在成为抗生素的有希望的替代品；然而，它们对特定宿主的特异性通常限制了它们的使用。在这项研究中,获得114个噬菌体的集合，并对238个临床肺炎克雷伯菌菌株进行分析，揭示了一系列裂解行为。推定的尾部蛋白簇与裂解模式之间的相关性导致发现了六个受体结合蛋白（RBP）簇，这些簇决定了宿主胶囊的嗜性。重要的是,鉴定了具有跨囊裂解能力的RBP。新识别的RBP提供了一个工具箱，用于定制针对不同胶囊类型的噬菌体。建立在工具箱上，具有改变的RBPs的工程噬菌体成功地改变并扩大了它们的宿主囊向性，为可调噬菌体奠定基础，为对抗肺炎克雷伯菌感染提供精确和灵活的解决方案。
