Combination Therapy of Phage vB_KpnM_P-KP2 and Gentamicin Combats Acute Pneumonia Caused by K47 Serotype Klebsiella pneumoniae

Abstract

<i>Klebsiella pneumoniae</i> (<i>K. pneumoniae</i>) is an important nosocomial and community acquired opportunistic pathogen which causes various infections. The emergence of multi-drug resistant (MDR) <i>K. pneumoniae</i> and carbapenem-resistant hypervirulent <i>K. pneumoniae</i> (CR-hvKP) has brought more severe challenge to the treatment of <i>K. pneumoniae</i> infection. In this study, a novel bacteriophage that specifically infects <i>K. pneumoniae</i> was isolated and named as vB_KpnM_P-KP2 (abbreviated as P-KP2). The biological characteristics of P-KP2 and the bioinformatics of its genome were analyzed, and then the therapeutic effect of P-KP2 was tested by animal experiments. P-KP2 presents high lysis efficiency <i>in vitro</i>. The genome of P-KP2 shows homology with nine phages which belong to "<i>KP15 virus</i>" family and its genome comprises 172,138 bp and 264 ORFs. Besides, P-KP2 was comparable to gentamicin in the treatment of lethal pneumonia caused by <i>K. pneumoniae</i> W-KP2 (K47 serotype). Furthermore, the combined treatment of P-KP2 and gentamicin completely rescued the infected mice. Therefore, this study not only introduces a new member to the phage therapeutic library, but also serves as a reference for other phage-antibiotic combinations to combat MDR pathogens.