Identification of a novel phage depolymerase against ST11 K64 carbapenem-resistant <i>Klebsiella pneumoniae</i> and its therapeutic potential

A novel phage vB_KpnP_IME1309 targeting ST11 K64 carbapenem-resistant <i>Klebsiella pneumoniae</i> (CRKP) was isolated and characterized. The ORF37 encoding depolymerase gene of phage vB_KpnP_IME1309 was successfully expressed and purified. Depolymerase increases the susceptibility of CRKP to serum killing, inhibits CRKP biofilm formation, and degrades mature biofilms. The combination of depolymerase and kanamycin is significantly more effective than either depolymerase or kanamycin alone in the treatment of CRKP biofilm. Depolymerase injection at 5 min and 2 h after CRKP infection of <i>Galleria mellonella</i> larvae increased the survival rate of larvae by up to 73% and 53%, respectively. Depolymerase Dep37 may be used as a method for the development of novel alternative therapeutic strategies against ST11 K64 CRKP.