Capsule-Targeting Depolymerase Promotes Sustained Immune-mediated Clearance of Multidrug-resistant Klebsiella pneumoniae

作者：Yicheng Wen, Yan Qian, Y U N F E N Yan, Jie Zhu, Qizhao Gao, Zhichen Zhu, Jingnan Lv, Yaxuan Zhai, Liang Wang, Liang Chen, H D Du · 发表于：Figshare · 年份：2026 · DOI：10.6084/m9.figshare.32740605.v4 · 研究领域：Microbiology、Immunology、Chemistry、Biology、Medicine

The rise of multidrug-resistant Klebsiella pneumoniae has severely limited the effectiveness of conventional antibiotics. While phages and derived depolymerases represent promising alternatives, their impact on infection dynamics remains poorly understood. Here, we identify a phage-derived depolymerase, Depo17, that efficiently degrades K64 capsular polysaccharides, thereby exposing the bacterial surface to immune recognition and markedly increasing susceptibility to phagocytosis and serum-mediated killing in vitro . We further evaluate the therapeutic efficacy through a time-course murine bacteremia model. In contrast to the rapid bacteriolysis characteristic of phage therapy, Depo17 treatment facilitates a more sustained bacterial clearance. This effect is particularly pronounced in the blood and liver, where the enhanced removal of decapsulated bacteria results in reduced inflammatory and tissue injury. These findings suggest depolymerase-mediated capsule removal attenuates bacterial virulence and facilitates host immune-mediated clearance, providing insight into the therapeutic potential of depolymerases against multidrug-resistant infections.