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In Vitro and In Vivo Assessments of Newly Isolated N4-like Bacteriophage against ST45 K62 Capsular-Type Carbapenem-Resistant Klebsiella pneumoniae : vB_kpnP_KPYAP-1.
- Source :
-
International journal of molecular sciences [Int J Mol Sci] 2024 Sep 04; Vol. 25 (17). Date of Electronic Publication: 2024 Sep 04. - Publication Year :
- 2024
-
Abstract
- The rise of carbapenem-resistant Klebsiella pneumoniae (CRKP) presents a significant global challenge in clinical and healthcare settings, severely limiting treatment options. This study aimed to utilize a bacteriophage as an alternative therapy against carbapenem-resistant K. pneumoniae . A novel lytic N4-like Klebsiella phage, vB&#95;kpnP&#95;KPYAP-1 (KPYAP-1), was isolated from sewage. It demonstrated efficacy against the K62 serotype polysaccharide capsule of bla <subscript>OXA-48</subscript> -producing K. pneumoniae . KPYAP-1 forms small, clear plaques, has a latent period of 20 min, and reaches a growth plateau at 35 min, with a burst size of 473 plaque-forming units (PFUs) per infected cell. Phylogenetic analysis places KPYAP-1 in the Schitoviridae family, Enquatrovirinae subfamily, and Kaypoctavirus genus. KPYAP-1 employs an N4-like direct terminal repeat mechanism for genome packaging and encodes a large virion-encapsulated RNA polymerase. It lacks integrase or repressor genes, antibiotic resistance genes, bacterial virulence factors, and toxins, ensuring its safety for therapeutic use. Comparative genome analysis revealed that the KPYAP-1 genome is most similar to the KP8 genome, yet differs in tail fiber protein, indicating variations in host recognition. In a zebrafish infection model, KPYAP-1 significantly improved the survival rate of infected fish by 92% at a multiplicity of infection (MOI) of 10, demonstrating its potential for in vivo treatment. These results highlight KPYAP-1 as a promising candidate for developing phage-based therapies targeting carbapenemase-producing K. pneumoniae .
- Subjects :
- Animals
Phylogeny
Genome, Viral
Carbapenems pharmacology
Carbapenem-Resistant Enterobacteriaceae genetics
Carbapenem-Resistant Enterobacteriaceae drug effects
Anti-Bacterial Agents pharmacology
Phage Therapy
Klebsiella pneumoniae virology
Klebsiella pneumoniae drug effects
Klebsiella pneumoniae genetics
Bacteriophages genetics
Bacteriophages physiology
Bacteriophages isolation & purification
Klebsiella Infections therapy
Klebsiella Infections microbiology
Zebrafish
Subjects
Details
- Language :
- English
- ISSN :
- 1422-0067
- Volume :
- 25
- Issue :
- 17
- Database :
- MEDLINE
- Journal :
- International journal of molecular sciences
- Publication Type :
- Academic Journal
- Accession number :
- 39273543
- Full Text :
- https://doi.org/10.3390/ijms25179595