Characterization of a Phage vB_LZ 2044 Deriving from K1-Type Hypervirulent Klebsiella pneumoniae Efficient Against Liver Infection Mice Model.

Abstract

In order to address the issue of antimicrobial resistance posed by hypervirulent Klebsiella pneumoniae (hvKp), bacteriophages that selectively target and lyse the bacteria are being investigated as a promising therapeutic option for the treatment of clinical infections associated with hvKp. The phage vB_LZ 2044, which was isolated and characterized utilizing hvKp NTUH-K2044 as the host strain, demonstrates significant efficacy against nine distinct K1 serotype Klebsiella pneumoniae strains and exhibits an impressive lysing capacity of 396.7 PFU/cell at burst size. Moreover, it displays remarkable stability across a wide pH range (pH 4-10) and temperature range (4-40 °C), positioning it as a promising antimicrobial agent. Genetic analysis has revealed that vB_LZ 2044 is a 50419 bp double-stranded DNA phage classified under the genus Webervirus within the family Drexlerviridae. The putative Open Reading Frames (ORFs) encoded by the phage, including the perforin-endolysin-spanin system protein (ORF26, ORF27, ORF28) and the peptin lyase folds containing the tailspike protein (ORF10), are crucial for lysing the host bacteria. Furthermore, experiments conducted on mice have demonstrated the effectiveness of vB_LZ 2044 in treating hvKp-induced liver infections without inflicting additional damage to the liver tissues, thus preserving the integrity of the liver structure and mitigating inflammation. The stable biological properties and pronounced antimicrobial effects observed in the mice model suggest that phage vB_LZ 2044 holds significant potential for development as a novel antimicrobial agent.