Characterization and Therapeutic Potential of a Novel Lytic Bacteriophage vB_Kp_H122 Targeting Multidrug‐Resistant Hypervirulent Klebsiella pneumoniae of K57 Capsular Type

Abstract

Klebsiella pneumoniae is an important zoonotic opportunistic pathogen. Of particular concern is the emergence of multidrug‐resistant hypervirulent K. pneumoniae (MDR‐hvKP), which represents a serious public health threat. Bacteriophage (phage) therapy has emerged as a promising solution to combat antibiotic‐resistant K. pneumoniae infections. Here, we characterize a novel lytic phage, vB_Kp_H122, that specifically targets K57 capsular‐type MDR‐hvKP. vB_Kp_H122 exhibited the characteristic morphology of a siphovirus and demonstrated efficient infection kinetics, with an optimal multiplicity of infection (MOI) of 0.001 and a latent period of ~5 min. It also demonstrated considerable stability across a pH range of 4–11 and at temperatures from 4°C to 50°C, as well as potent activity against K. pneumoniae biofilms. The phage has a linear double‐stranded DNA genome of 46,077 bp with a G + C content of 47.61% and belongs to a novel species within the genus Roufvirus. Its genome contained no identifiable genes associated with lysogeny, virulence, or antibiotic resistance, supporting its therapeutic safety. In a mouse infection model, a single dose of vB_Kp_H122 at 2 × 106 PFU significantly reduced bacterial loads in organs, alleviated pathological damage, and provided complete protection against lethal challenge with K57 MDR‐hvKP. These findings suggest that vB_Kp_H122 may have potential as an antibacterial candidate against K57 MDR‐hvKP isolates.