Isolation, characterization, therapeutic potential and depolymerase identification of a lytic bacteriophage Kpp-9 against Klebsiella pneumoniae with capsule serotype K2.

Abstract

Klebsiella pneumoniae is one of the most threatening multidrug-resistant bacteria, and its inherent capsule and extensive biofilm formation pose a significant barrier to the treatment of infection. Bacteriophages (or phages) and phage-derived depolymerases are attracting attention as potential alternatives to antibiotics. Here, we isolated a lytic phage, named Kpp-9, using a capsule-type K2 strain, Kp09. Kpp-9 could inhibit bacterial biofilm formation, eradicate the mature biofilm in vitro, improve the survival rate of Kp09-infected mice, and alleviate the symptoms of pneumonia in mice. Morphological and genomic analyses showed that phage Kpp-9 belonged to the class Caudoviricetes and no virulence or resistance genes were found in the genome, indicating potential therapeutic applications of phage Kpp-9. Furthermore, two depolymerases (Kp9042 and Kp9050) were predicted and shown to be able to digest the capsule and improve the susceptibility of K. pneumoniae to complement-mediated serum killing. In addition, Kpp-9 and two depolymerases showed high selectivity for capsule-type K2 K. pneumoniae strains and exhibited robust thermal and pH stability. These results demonstrate that phage Kpp-9 and its encoded depolymerases Kp9042 and Kp9050 may serve as alternative therapeutic agents for the treatment of capsule-type K2 K. pneumoniae infections.