Phage Selective Pressure Reduces Virulence of Hypervirulent Klebsiella pneumoniae Through Mutation of the wzc Gene

Hypervirulent Klebsiella pneumoniae (hvKp), one of the major community-acquired pathogens, can cause invasive infections such as liver abscess. In recent years, bacteriophages have been used in the treatment of K. pneumoniae, but the characteristics of the phage-resistant bacteria produced in the process of phage therapy need to be evaluated. In this study, two Podoviridae phages, hvKpP1 and hvKpP2, were isolated and characterized. In vitro and in vivo experiments demonstrated that the virulence of the resistant bacteria was significantly reduced compared with that of the wild type. Comparative genomic analysis of monoclonal sequencing showed that nucleotide deletion mutations of wzc and wcaJ genes led to phage resistance, and the electron microscopy and mucoviscosity results showed that mutations led to the loss of the capsule. Meanwhile, animal assay indicated that loss of capsule reduced the virulence of hvKp. These findings contribute to a better understanding of bacteriophage therapy, which not only can kill bacteria directly but also can reduce the virulence of bacteria by phage screening.

Automated summary

This study isolated and characterized two Podoviridae phages, hvKpP1 and hvKpP2, which were used in bacteriophage therapy against Klebsiella pneumoniae. Through in vitro and in vivo experiments, it was found that the resistant bacteria produced during phage therapy had significantly reduced virulence due to nucleotide deletion mutations in wzc and wcaJ genes, leading to loss of capsule and decreased virulence. These findings contribute to a better understanding of bacteriophage therapy and its potential in reducing bacterial virulence.