Abstract
The increasing incidence of carbapenemase-producing K. pneumoniae strains (CP-Kps) in the last decade has become a serious global healthcare problem. Therapeutic options for the treatment of emerging hospital clones have drastically narrowed and therefore novel approaches must be considered. Here we have isolated and characterized a lytic bacteriophage, named vB_KpnS_Kp13, that was effective against all Verona integron-encoded metallo-β-lactamase (VIM) producing K. pneumoniae isolates originating from hospital samples (urine, blood, sputum and faeces), belonging to the ST15 clonal lineage and expressing the K24 capsule. Morphological characterization of vB_KpnS_Kp13 showed that the newly identified phage belonged to the Siphoviridae family, and phylogenetic analysis showed that it is part of a distinct clade of the Tunavirinae subfamily. Functional analysis revealed that vB_KpnS_Kp13 had relatively short latent period times (18 minutes) compared to other K. pneumoniae bacteriophages and could degrade biofilm by more than 50% and 70% in 24 and 48 hours respectively. Complete in vivo rescue potential of the new phage was revealed in an intraperitoneal mouse model where phages were administered intraperitoneally 10 minutes after bacterial challenge. Our findings could potentially be used to develop specific anti-CP-Kps bacteriophage-based therapeutic strategies against major clonal lineages and serotypes.
Highlights
Klebsiella pneumoniae is one of the most important opportunistic nosocomial pathogens, able to colonize the skin and mucosae of humans and cause urinary tract infections, septicaemia and pneumonia, predominantly in immunocompromised individuals[1,2]
The K24 serotype was recently reported to be frequently associated with ST159,17,18 and frequently reported from other carbapenemase-producing Klebsiella pneumoniae strains (CP-Kps)[25]
13 bacteriophages were isolated from wastewater against K. pneumoniae hospital isolates
Summary
Klebsiella pneumoniae is one of the most important opportunistic nosocomial pathogens, able to colonize the skin and mucosae of humans and cause urinary tract infections, septicaemia and pneumonia, predominantly in immunocompromised individuals[1,2]. Dissemination of antibiotic resistance, to carbapenem, is associated with highly diverse isolates of K. pneumoniae In this process the importance of certain clonal groups (CGs) such as CG258 and CG15 has been demonstrated. One potential option to combat these pathogens is to use bacteriophages as they have well defined target spectrums, characterized by host range specificity[19]. This feature makes them suitable therapeutic agents without influencing the normal microbiota of the patient[20]. Certain bacteriophages have the capacity to target and destroy defined capsular types and weaken biofilm typically produced by Klebsiella pneumoniae[21]. Our results may aid the development of anti CP-Kps bacteriophage-based therapeutic strategies targeting major clonal lineages
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