Two tail protein-derived capsule depolymerases from phage vB_KpnS_GH-K1 are effective against pneumonia caused by K2 serotype Klebsiella pneumoniae.

Hypervirulent Klebsiella pneumoniae (hvKP) poses an escalating threat to public health and animal husbandry. In this study, we isolated and characterized the bacteriophage vB_KpnS_GH-K1 (GH-K1) of "KP36likevirus" genus, and identified two phage-derived depolymerases: tail fiber protein-TFP41 and tail spike protein-TSP42. Both depolymerases exhibited potent activity in degrading the capsular polysaccharides (CPS) of K2 serotype K. pneumoniae. Capsule degradation by TFP41 and TSP42 enhances macrophage-mediated phagocytosis of K2 serotype strains, leading to potentiated activation of the mitogen-activated protein kinase (MAPK) signaling pathway. In vivo experiments demonstrated the exceptional therapeutic efficacy of TSP42, where a single 20 μg dose ensured over 80% survival in mice within 12 h of intranasal infection, achieving complete survival when administered within 2 h. Importantly, TSP42 demonstrates superior therapeutic efficacy against acute pneumonia caused by K2 strains compared to other depolymerases in "KP36likevirus". Although TFP41 exhibited slightly weaker efficacy, daily administration for three consecutive days also resulted in 100% survival, and notably represents the first tail fiber depolymerase with demonstrated therapeutic efficacy in the "KP36likevirus" genus, expanding the functional diversity of phage-derived depolymerases beyond well-characterized tail spike proteins. These findings underscore the potential of phage-derived depolymerases as innovative therapeutic agents against hvKP infections and position TSP42 as an exceptionally promising antibiotic alternative.

• Publication year

  2025

• Venue

  International Journal of Antimicrobial Agents

• Publication date

  2025-11-01

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1016/j.ijantimicag.2025.107662PMID 41197965
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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