Data-Driven Engineering of Phages with Tunable Capsule Tropism for Klebsiella pneumoniae

针对肺炎克雷伯菌的可调荚膜趋向性噬菌体的数据驱动工程

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作者:Chao Wang, Shiwei Wang, Shisong Jing, Yuan Zeng, Lili Yang, Yongqi Mu, Zixuan Ding, Yuqin Song, Yanmei Sun, Gang Zhang, Dawei Wei, Ming Li, Yingfei Ma, Haijian Zhou, Linhuan Wu, Jie Feng

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.

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