φBO1E, a newly discovered lytic bacteriophage targeting carbapenemase-producing Klebsiella pneumoniae of the pandemic Clonal Group 258 clade II lineage

Abstract

The pandemic dissemination of KPC carbapenemase-producing Klebsiella pneumoniae (KPC-KP) represents a major public health problem, given their extensive multidrug resistance profiles and primary role in causing healthcare-associated infections. This phenomenon has largely been contributed by strains of Clonal Group (CG) 258, mostly of clade II, which in some areas represent the majority of KPC-KP isolates. Here we have characterized a newly discovered lytic Podoviridae, named φBO1E, targeting KPC-KP strains of clade II lineage of CG258. Genomic sequencing revealed that φBO1E belongs to the Kp34virus genus (87% nucleotide identity to vB_KpnP_SU552A). ΦBO1E was stable over a broad pH and temperature range, exhibited strict specificity for K. pneumoniae strains of clade II of CG258, and was unable to establish lysogeny. In a Galleria mellonella infection model, φBO1E was able to protect larvae from death following infection with KPC-KP strains of clade II of CG258, including one colistin resistant strain characterized by a hypermucoviscous phenotype. To our best knowledge φBO1E is the first characterized lytic phage targeting K. pneumoniae strains of this pandemic clonal lineage. As such, it could be of potential interest to develop new agents for treatment of KPC-KP infections and for decolonization of subjects chronically colonized by these resistant superbugs.

Identification of a newly isolated lytic bacteriophage against K24 capsular type, carbapenem resistant Klebsiella pneumoniae isolates

“…The latent period time (18 min) of phage vB_KpnS_Kp13 was longer that of Klebsiella phage ϕBO1E (Podoviridae; 10 min) 35 . The burst size of vB_KpnS_Kp13 (~220 phage particles/infected cell) was not extremely high compared with two phages in the Siphoviridae 36 and Podoviridae 35 families, but they assured an effective bactericidal potential as vB_KpnS_Kp13 could prevent proliferation of its target bacterium from an MOI of 0.01. Compared to phage TSK1 21 , this value was lower by 2 orders of magnitude and therefore was more effective.…”

Complete genome analysis of a Siphoviridae phage TSK1 showing biofilm removal potential against Klebsiella pneumoniae

“…pneumoniae specific bacteriophage TSK1 has the distinctive character to form opaque halo zone surrounding the clear zone of plaque. The hazy halo zones suggest the ability of TSK1 phage to produce soluble, polysaccharide-degrading enzymes 20 . Previous research showed that the formation of halo zones is an indicator for the presence of phage tail-associated exopolysaccharide (EPS) depolymerases 9 .…”

Characterization of vB_Kpn_F48, a Newly Discovered Lytic Bacteriophage for Klebsiella pneumoniae of Sequence Type 101

“…The dynamic change in phage particles number during a replicative cycle was monitored to determine the latency period, the eclipse period and the burst size of vB_Kpn_F48 as previously described [ 28 ] with minor modifications. Briefly, the host strain 12C47 was grown in aerobic conditions at 37 °C to mid-exponential phase (OD 600 = 0.3–0.4, corresponding to ≈1–2 × 10 8 CFU/mL).…”