PMID- 37612659 OWN - NLM STAT- MEDLINE DCOM- 20230825 LR - 20231122 IS - 1471-2180 (Electronic) IS - 1471-2180 (Linking) VI - 23 IP - 1 DP - 2023 Aug 23 TI - Characterization of novel bacteriophage PSKP16 and its therapeutic potential against beta-lactamase and biofilm producer strain of K2-Hypervirulent Klebsiella pneumoniae pneumonia infection in mice model. PG - 233 LID - 10.1186/s12866-023-02979-7 [doi] LID - 233 AB - BACKGROUND: Severe infections caused by beta- 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-alpha (TNF alpha). 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. CI - (c) 2023. BioMed Central Ltd., part of Springer Nature. FAU - Rahimi, Sara AU - Rahimi S AD - Medical Microbiology Research Center, Qazvin University of Medical Sciences, Qazvin, Iran. AD - Student Research Committee, Qazvin University of Medical Sciences, Qazvin, Iran. FAU - Bakht, Mehdi AU - Bakht M AD - Medical Microbiology Research Center, Qazvin University of Medical Sciences, Qazvin, Iran. AD - Student Research Committee, Qazvin University of Medical Sciences, Qazvin, Iran. FAU - Javadi, Amir AU - Javadi A AD - Medical Microbiology Research Center, Qazvin University of Medical Sciences, Qazvin, Iran. AD - Department of Community Medicine, Qazvin University of Medical Sciences, Qazvin, Iran. FAU - Foroughi, Farshad AU - Foroughi F AD - Medical Microbiology Research Center, Qazvin University of Medical Sciences, Qazvin, Iran. AD - Department of Immunology, School of Medicine, Qazvin University of Medical Sciences, Qazvin, Iran. FAU - Marashi, Seyed Mahmoud Amin AU - Marashi SMA AD - Medical Microbiology Research Center, Qazvin University of Medical Sciences, Qazvin, Iran. FAU - Nikkhahi, Farhad AU - Nikkhahi F AD - Medical Microbiology Research Center, Qazvin University of Medical Sciences, Qazvin, Iran. Farhadnikkhahi@gmail.com. LA - eng PT - Journal Article DEP - 20230823 PL - England TA - BMC Microbiol JT - BMC microbiology JID - 100966981 RN - 0 (Gentamicins) SB - IM MH - Animals MH - Mice MH - *Bacteriophages/genetics MH - Klebsiella pneumoniae MH - Inflammation MH - Biofilms MH - Disease Models, Animal MH - Gentamicins PMC - PMC10464470 OTO - NOTNLM OT - Bacteriophage OT - Biofilm OT - Hypervirulent OT - Klebsiella pneumoniae OT - Mice model OT - beta-lactamase COIS- The authors declare no competing interests. EDAT- 2023/08/24 00:42 MHDA- 2023/08/25 06:42 PMCR- 2023/08/23 CRDT- 2023/08/23 23:40 PHST- 2023/04/22 00:00 [received] PHST- 2023/08/14 00:00 [accepted] PHST- 2023/08/25 06:42 [medline] PHST- 2023/08/24 00:42 [pubmed] PHST- 2023/08/23 23:40 [entrez] PHST- 2023/08/23 00:00 [pmc-release] AID - 10.1186/s12866-023-02979-7 [pii] AID - 2979 [pii] AID - 10.1186/s12866-023-02979-7 [doi] PST - epublish SO - BMC Microbiol. 2023 Aug 23;23(1):233. doi: 10.1186/s12866-023-02979-7.