Abstract
Klebsiella pneumoniae (K. pneumoniae) is an important nosocomial and community acquired opportunistic pathogen which causes various infections. The emergence of multi-drug resistant (MDR) K. pneumoniae and carbapenem-resistant hypervirulent K. pneumoniae (CR-hvKP) has brought more severe challenge to the treatment of K. pneumoniae infection. In this study, a novel bacteriophage that specifically infects K. pneumoniae 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 in vitro. The genome of P-KP2 shows homology with nine phages which belong to “KP15 virus” 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 K. pneumoniae 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.
Highlights
As the second-ranked nosocomial infection-causing-pathogens, Klebsiella pneumoniae (K. pneumoniae) causes fatal systemic infections (Paczosa and Mecsas, 2016)
The host lysis system of P-KP2 is composed of four parts, T holin lysis mediator (ORF48), spanin (ORF123 and ORF124), antiholin (ORF180), and endolysin (ORF197), which is consistent with the characteristics of the lysis modules of “KP15likevirus” genus (Zhao et al, 2019)
The threat of multi-drug resistant (MDR) K. pneumoniae to public health in humans, especially in immunocompromised populations, and its evolution toward carbapenem-resistant hypervirulent K. pneumoniae (CR-hypervirulent K. pneumoniae (hvKP)) have led to increased public recognition in the substitution or synergism of phage therapy for antibiotics
Summary
As the second-ranked nosocomial infection-causing-pathogens, Klebsiella pneumoniae (K. pneumoniae) causes fatal systemic infections (Paczosa and Mecsas, 2016). It has been reported that there are more than 1031 phage particles in the biosphere This massive phage diversity has a marked effect on the environment, ecology, and bacterial evolution (Davies et al, 2016). Owing to their specific bactericidal abilities, phages have been considered as therapeutic agents since the early 1920s. The combination therapy of phage and antibiotics can effectively increase the sensitivity of target strains to antibiotics and reduce the probability of phage resistance mutations, thereby providing a development direction for controlling bacterial infections caused by MDR strains (Abedon, 2019)
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