Abstract

Resistance to carbapenems in Enterobacteriaceae, including Klebsiella pneumoniae, represents a major clinical problem given the lack of effective alternative antibiotics. Bacteriophages could provide a valuable tool to control the dissemination of antibiotic resistant isolates, for the decolonization of colonized individuals and for treatment purposes. In this work, we have characterized a lytic bacteriophage, named vB_Kpn_F48, specific for K. pneumoniae isolates belonging to clonal group 101. Phage vB_Kpn_F48 was classified as a member of Myoviridae, order Caudovirales, on the basis of transmission electron microscopy analysis. Physiological characterization demonstrated that vB_Kpn_F48 showed a narrow host range, a short latent period, a low burst size and it is highly stable to both temperature and pH variations. High throughput sequencing and bioinformatics analysis revealed that the phage is characterized by a 171 Kb dsDNA genome that lacks genes undesirable for a therapeutic perspective such integrases, antibiotic resistance genes and toxin encoding genes. Phylogenetic analysis suggests that vB_Kpn_F48 is a T4-like bacteriophage which belongs to a novel genus within the Tevenvirinae subfamily, which we tentatively named “F48virus”. Considering the narrow host range, the genomic features and overall physiological parameters phage vB_Kpn_F48 could be a promising candidate to be used alone or in cocktails for phage therapy applications.

Highlights

  • The extensive usage of antibiotics has led to the emergence and dissemination of antibiotic resistant bacteria, with an increasing number of reports in hospital settings of strains showing multidrug resistant (MDR), extremely drug resistant (XDR), or even pandrug resistant (PDR)phenotypes [1]

  • We describe the isolation and characterization of a novel bacteriophage of the Myoviridae family with a lytic activity specific to K. pneumoniae strains belonging to ST101 and other members of CG101

  • The spread of antibiotic-resistant pathogens constitutes a serious matter in the clinical setting, given the scarcity of available treatment options

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Summary

Introduction

The extensive usage of antibiotics has led to the emergence and dissemination of antibiotic resistant bacteria, with an increasing number of reports in hospital settings of strains showing multidrug resistant (MDR), extremely drug resistant (XDR), or even pandrug resistant (PDR)phenotypes [1]. Klebsiella pneumoniae has emerged as one of the most challenging antibiotic-resistant pathogens, since it can cause a variety of infections (e.g., urinary tract infections, pneumonia, intra-abdominal infections, surgical site infections, bacteremia) and exhibits a remarkable propensity to acquire MDR and XDR phenotypes. Some clonal lineages of K. pneumoniae have acquired resistance determinants to most antibiotics available for treating these infections, including fluoroquinolones, aminoglycosides, expanded-spectrum cephalosporins and carbapenems, while retaining a notable propensity to disseminate in healthcare settings.

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