Characterization of novel bacteriophage PSKP16 and its therapeutic potential against β-lactamase and biofilm producer strain of K2-Hypervirulent Klebsiella pneumoniae pneumonia infection in mice model

Abstract

Background Severe infections caused by β- lactamase producers, hypervirulent Klebsiella pneumoniae (BhvKp) with K2 serotype, highlight emergency need for new therapeutic strategies against this pathogen. We aimed to assess the efficacy of a novel phage, PSKP16, in the treating of pneumonia induced by BhvKp in mice models. Method Genome sequences of PSKP16 were analyzed, and associated information can be found in NCBI. We applied treatment in two ways: by using mice for immediate and delayed treatments. Moreover, acute pneumonia obtained by BhvKp with intranasal method, was characterized in terms of histopathology of pulmonary lesions, biomarkers of inflammation level, leukocytes cells infiltration extent in mice, and was assessed treatment of them with PSKP16 multiplicity of infection (MOI: 10), either individually or in combination with gentamicin. Assessment of the ability of PSKP16 to inhibit BhvKp biofilm was studied. Results PSKP16 was associated with the Drexlerviridae family, and had a genome size of 46,712 bp, and 67 predicted ORFs. Herein, prompt phage administration’s efficacy to decrease bacterial load and improve the survival rate in pneumonia models was faster than the synergism model with delay, but both almost displayed similar endpoints. The distribution of BhvKp strains in the lung was consistent with the histopathological findings, simultaneous inflammation, and level of serum tumor necrosis factor-α (TNF α). The phage treatment presented a lack of severe lesions and alveolar edema, reduction of inflammatory cell infiltration, which not only was it not associated with an over-inflammation but also provided a faster correction of blood cell count abnormalities compared to gentamicin. Phage with a high concentration in in vitro model effectively eliminated biofilms. Conclusion It is essential to raise clinical awareness and management of BhvKp infections, signaled as the next superbug in waiting. The results of our study underscore the importance of PSKP16 as a phage with promising therapeutic potential in treating BhvKp-induced pneumonia.

A Review of colistin-resistant Escherichia coli isolates in Middle East: Mechanisms, epidemiology, and dissemination from different origins in human, animal, food, and soil

“…In this study, most colistin-resistant E. coli isolates were found to have plasmid -mediated colistin resistance, mcr genes (especially mcr-1), compared with mutations in the pmrAB, phoPQ, and mgrB genes, in contrast to Klebsiella spp. There are new strategies to control MDR/XDR/PDR bacteria, including phage therapy, nanoparticles, aptamer, and combination therapy (48). According to some studies, the appropriate use of disinfectants (sodium hypochlorite 5%, chloroxylenol (Dettol) 4.8%, Sayasept-HP 2%, chlorhexidine 2%, and ethanol 70%) at the right concentrations for the different bacterial species should also be considered to avoid the induction of resistance mechanisms in bacteria (49).…”

Relationship between biofilm formation and antibiotic resistance of Klebsiella pneumoniae and updates on antibiofilm therapeutic strategies

“…Asif et al isolated a K-17 serotype specific K. pneumoniae phage JKP2, which could significantly eliminate preformed biofilms with a rate of 98% for 24-hour-old biofilm, 96% of 48-hour-old biofilm, 86% and 82% for mature biofilm on day 3 and 4, respectively (Asif et al, 2023). Rahimi et al characterized a lytic phage PSKP16 with therapeutic potential against b-lactamase and biofilm producing K2-Hypervirulent K. pneumoniae using a mouse pneumonia model (Rahimi et al, 2023). PSKP16 could reduce 18-64.6% of the 24hour-old biofilms and 16.4-63.7% of the 48-hour-old biofilms.…”

Therapeutic efficacy of a K5-specific phage and depolymerase against Klebsiella pneumoniae in a mouse model of infection

“…Some reports have proven the effectiveness of antibacterial phages against Klebsiella [ 13 , 14 ] . However, most studies on Klebsiella phages have focused predominantly on the K1, K2 and KL64 serotypes [ 15 , 16 ]. The evaluation of phage antibacterial properties against K5 K. pneumoniae remains scarce and limited to only one existing assessment [ 17 ].…”