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Isolation and Characterization of vB_kpnM_17-11, a Novel Phage Efficient Against Carbapenem-Resistant Klebsiella pneumoniae

Jiawei Bai, Feiyang Zhang, Shuang Liang, Qiao Chen, Wei Wang, Ying Wang, Alberto J. Martín‐Rodríguez, Åsa Sjöling, Renjing Hu, Yingshun Zhou

2022Frontiers in Cellular and Infection Microbiology45 citationsDOIOpen Access PDF

Abstract

Phages and phage-encoded proteins exhibit promising prospects in the treatment of Carbapenem-Resistant Klebsiella pneumoniae (CRKP) infections. In this study, a novel Klebsiella pneumoniae phage vB_kpnM_17-11 was isolated and identified by using a CRKP host. vB_kpnM_17-11 has an icosahedral head and a retractable tail. The latent and exponential phases were 30 and 60 minutes, respectively; the burst size was 31.7 PFU/cell and the optimal MOI was 0.001. vB_kpnM_17-11 remained stable in a wide range of pH (4-8) and temperature (4-40°C). The genome of vB_kpnM_17-11 is 165,894 bp, double-stranded DNA (dsDNA), containing 275 Open Reading Frames (ORFs). It belongs to the family of Myoviridae , order Caudovirales, and has a close evolutionary relationship with Klebsiella phage PKO111. Sequence analysis showed that the 4530 bp orf022 of vB_kpnM_17-11 encodes a putative depolymerase. In vitro testing demonstrated that vB_kpnM_17-11 can decrease the number of K. pneumoniae by 10 5 -fold. In a mouse model of infection, phage administration improved survival and reduced the number of K. pneumoniae in the abdominal cavity by 10 4 -fold. In conclusion, vB_kpnM_17-11 showed excellent in vitro and in vivo performance against K. pneumoniae infection and constitutes a promising candidate for the development of phage therapy against CRKP.

Topics & Concepts

Klebsiella pneumoniaeMyoviridaePhage therapyMicrobiologyLytic cycleBiologyBacteriophageORFSIn vivoVirologyEscherichia coliGeneOpen reading frameVirusPeptide sequenceGeneticsBacteriophages and microbial interactionsGenomics and Phylogenetic StudiesMicrobial infections and disease research