A capsule-dependent lytic phage for targeting multidrug-resistant and hypervirulent Klebsiella pneumoniae

TL;DR

This study introduces a phage called phiK2044 that effectively targets dangerous, drug-resistant Klebsiella pneumoniae strains and works well in mice without harmful side effects.

Contribution

The discovery of phiK2044, a lytic phage with high specificity for hypervirulent K. pneumoniae and a novel wcaJ-dependent binding mechanism.

Findings

PhiK2044 showed strong efficacy against hypervirulent K. pneumoniae subtypes in both in vitro and in vivo models.

The phage binds to the host via the wcaJ gene, which is essential for capsular synthesis.

PhiK2044 safely cleared bacterial infections in mice without significant side effects.

Abstract

As the threat of multidrug-resistant Klebsiella pneumoniae strains rises, the potential of phages as promising alternatives to antibiotics is increasingly being demonstrated. In this study, we isolated and characterized phiK2044, a highly specific and efficient lytic phage targeting the model strain K. pneumoniae NTUH-K2044. Demonstrating wide host compatibility, potent lytic activity, and robust environmental adaptability, phiK2044 exhibited exceptional efficacy against hypervirulent subtypes, including hypervirulent K. pneumoniae (45.2%), sequence type 23 (87.5%), and capsular K1 (92.3%). In the mouse model, phiK2044 effectively cleared bacteria without significant side effects, highlighting its therapeutic potential. Mechanistically, we identified wcaJ, a gene encoding a glycosyltransferase essential for capsular synthesis, as the critical determinant of the binding of phiK2044 to the host. Beyond its clinical utility, phiK2044 represents a model for studying phage ecology, host–microbe interactions, and capsule-dependent tropism. Collectively, phiK2044 represents a valuable tool against ST23/K1 K. pneumoniae infections, such as liver abscesses and bacteremia.

The rise of multidrug-resistant Klebsiella pneumoniae demands innovative therapies. This study identifies phiK2044, a lytic phage with high specificity and efficacy against hypervirulent subtypes. It safely clears infections in mice and reveals wcaJ-dependent capsule synthesis as the key host interaction mechanism. Beyond its therapeutic promise, phiK2044 serves as a critical tool for studying phage-host dynamics and capsule-mediated tropism, bridging clinical solutions and fundamental research in combating antimicrobial resistance.

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