Analysis of a novel phage as a promising biological agent targeting multidrug resistant Klebsiella pneumoniae.

Abstract

The rise of deaths by resistant bacteria is a global threat to public health systems. Klebsiella pneumoniae is a virulent pathogen that causes serious nosocomial infections. The major obstacle to bacterial treatment is antibiotic resistance, which necessitates the introducing of alternative therapies. Phage therapy has been regarded as a promising avenue to fight multidrug-resistant (MDR) pathogens. In the current study, a novel phage vB_KpnP_KP17 was isolated from sewage, and its lytic potential was investigated against K. pneumoniae. The isolated phage vB_KpnP_kP17 was lytic to 17.5% of tested K. pneumoniae isolates. One step growth curve indicated a virulent phage with a short latent period (20 min) and large burst size (331 PFU/cell). Additionally, vB_KpnP_kP17 maintained its activity against planktonic cells over a wide range of pH, temperature and UV irradiation intervals. The potential of vB_KpnP_KP17 as antibiofilm agent was revealed by the biofilm inhibition assay. The isolated phage vB_KpnP_KP17 at multiplicity of infection (MOI) of 10 inhibited more than 50% of attached biofilms of tested K. pneumoniae isolates. The genome of vB_KpnP_kP17 was characterized and found to be a linear dsDNA of 39,936 bp in length and GC content of 52.85%. Additionally, the absence of toxicity, virulence and antibiotic resistance genes further confirms the safety of vB_KpnP_KP17 for clinical applications. These characteristics make vB_KpnP_KP17 of a potential therapeutic value to manage MDR K. pneumoniae infections. Additionally, the formulation of vB_KpnP_KP17 in a cocktail with other lytic phages or with antibiotics could be applied to further limit biofilm-producing K. pneumoniae infections.