Identification and complete genome of lytic “Kp34likevirus” phage vB_KpnP_Bp5 and therapeutic potency in the treatment of lethal Klebsiella pneumoniae infections in mice

Abstract

Klebsiella pneumoniae (K. pneumoniae) infection exist widely in the farming and medical. The treatment of K. pneumoniae infection is primarily based on antibiotics, which not only leads to a large economic burden but also the development of antibiotic resistance. Bacteriophages therapy present a promising alternative. The object of this study was identifying comprehensively a lytic lethal K. pneumoniae phage vB_KpnP_Bp5, and evaluating the phage as an anti-infective agent in an experimental K. pneumoniae infection murine model. The phage Bp5 had the following characteristics: the optimal number of infections was 0.001, the latent period was 5 min, the outbreak period was 40 min, the burst size was 24 plaque-forming unit (PFU)/cell, the phage could withstand 50 °C temperature and the optimal pH value was 4.0–10.0. According to electron microscopy and whole-genome sequence analysis, the phage should be classified as a member of order Caudovirales, family Podoviridae, subfamily Autographiviridae. Meantime, phylogenetic analysis showed high conservation of gene arrangement and gene content. We demonstrated that administration of phage Bp5 significantly reduced colony formation by K. pneumoniae and alleviated damage to lung tissue. In addition, different therapy time point was closely related to body health and the degree of tissue damage. Once treated promptly, it will greatly reduce mortality and alveolar inflammatory exudation and injury.