Journal Article

Characterization of a Phage-Encoded Depolymerase Against Klebsiella pneumoniae K30 Capsular Type and Its Therapeutic Application in a Murine Model of Aspiration Pneumonia

Feng, Yanling, Ke, Yuehua, Gan, Lin, Chen, Yuchen, Li, Zhoufei, Yang, Yang, Cui, Xiaohu, Yan, Chao, Feng, Junxia, Cui, Jinghua, Fu, Tongtong, Xue, Guanhua, Zhao, Hanqing, Yu, Zihui, Xu, Ziying, Yuan, Jing, Fan, Zheng

2025

Overview

Capsular polysaccharides are critical virulence factors of Klebsiella pneumoniae, enabling the bacterium to evade host immune recognition and exacerbate infection. Phage-derived depolymerases, which specifically degrade these capsular polysaccharides, are increasingly recognized as a highly promising strategy for the treatment of bacterial infections. In the present study, we isolated and characterized a lytic Klebsiella pneumoniae phage, named phiTH1, and sequenced its genome. The K30-type capsular polysaccharide was identified as the receptor for phiTH1 infection. A tail fiber protein with a pectate lyase domain, Dop5, was then recognized as a potential K30-type depolymerase. Therefore, the recombinant protein Dop5 was expressed in Escherichia coli and purified, and its in vitro capsular depolymerase activity was demonstrated. Further, by using a murine aspiration pneumonia model induced by K30-type Klebsiella pneumoniae TH1, we found that Dop5 protected 80% of mice from lethal challenge with Klebsiella pneumoniae. After Dop5 treatment, the pathological damage in multiple organs of mice was alleviated, the bacterial load was reduced, and serum levels of inflammatory cytokines and complement C3 decreased, along with a significant reduction in the pathological score of the lungs. Hence, this study revealed the potential of the depolymerase Dop5 for the treatment of Klebsiella pneumoniae infections.

• Publisher: MDPI AG
• Subject: Animal models / Animals / Antibiotics / Aspiration pneumonia / Bacteria / Bacterial Capsules - metabolism / Bacterial infections / Bacteriophages - enzymology / Bacteriophages - genetics / capsular polysaccharide / Capsular polysaccharides / Complement component C3 / depolymerase / Disease Models, Animal / Female / Genomes / Genomics / Glycoside Hydrolases - genetics / Health aspects / Hemodialysis / Infection / Klebsiella Infections - drug therapy / Klebsiella Infections - microbiology / Klebsiella Infections - therapy / Klebsiella pneumoniae / Klebsiella pneumoniae - drug effects / Klebsiella pneumoniae - virology / Lymphocytes T / Medical research / Medicine, Experimental / Mice / Mutation / Pathogens / Pectate lyase / phage / Phages / Pneumonia / Pneumonia, Aspiration - drug therapy / Pneumonia, Aspiration - microbiology / Pneumonia, Aspiration - therapy / Polysaccharides / Recombinant proteins / Serum levels / Tail fiber protein / Transmission electron microscopy / Virulence / Virulence factors