In Vitro and In Vivo Assessments of Newly Isolated N4-like Bacteriophage against ST45 K62 Capsular-Type Carbapenem-Resistant <i>Klebsiella pneumoniae</i>: vB_kpnP_KPYAP-1

oleh: Shanmuga Priya Natarajan, Soon-Hian Teh, Ling-Chun Lin, Nien-Tsung Lin

Format: Article
Diterbitkan: MDPI AG 2024-09-01

Deskripsi

The rise of carbapenem-resistant <i>Klebsiella pneumoniae</i> (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 <i>K. pneumoniae</i>. A novel lytic N4-like <i>Klebsiella</i> phage, vB_kpnP_KPYAP-1 (KPYAP-1), was isolated from sewage. It demonstrated efficacy against the K62 serotype polysaccharide capsule of <i>bla</i><sub>OXA-48</sub>-producing <i>K. pneumoniae</i>. 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 <i>Schitoviridae</i> family, <i>Enquatrovirinae</i> subfamily, and <i>Kaypoctavirus</i> 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 <i>K. pneumoniae</i>.