Journal of Infection and Public Health
A novel
Door Hanyu Fu, Zihe Zhou, Zhiheng Tang en 7 anderen.
Inhoud in het Engels
Abstract
Background
Bacteriophages represent a promising alternative for combating carbapenem-resistant hypervirulent Klebsiella pneumoniae (Kp). However, the molecular mechanisms underlying phage-host co-evolution and the action of phage-derived anti-virulence effectors remain insufficiently explored. We hypothesized that a novel Przondovirus phage could suppress Kp virulence through receptor-mediated evolutionary trade-offs and disruption of metabolic pathways.
Methods
A novel phage, P1524, was isolated from hospital sewage and characterized using transmission electron microscopy, one-step growth curve analysis, and stability testing. Its host range was evaluated against 86 clinical Kp isolates. Phage-resistant mutants were generated and analyzed through whole-genome sequencing. Three phage-encoded effectors (Orf4, Orf15, Orf23) were cloned and expressed in Kp, followed by assessments of bacterial growth, biofilm formation, serum resistance, and in vivo survival in a Galleria mellonella model. Quantitative proteomics and quantitative real-time polymerase chain reaction (RT-qPCR) were conducted to identify host metabolic pathways targeted by these effectors.