ArticleBMC microbiology2026
Protective effects of recombinant depolymerase Dep44 against K64-CRKP-induced pulmonary infection in a murine infection model.
Article in BMC microbiology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundCarbapenem-resistant Klebsiella pneumoniae (CRKP) represents a critical public health challenge due to limited treatment options. Among CRKP serotypes, K64 has emerged as the most prevalent in China. This study aimed to isolate and characterize a phage specific for K64-CRKP and assess the protective efficacy of the depolymerase derived from this phage against CRKP-induced pulmonary infection in murine infection model, thereby establishing a scientific foundation for depolymerase-based therapeutic interventions. In this study, we isolated phage vB_Kpn_HF1013 capable of lysing K64-CRKP from hospital sewage and constructed its depolymerase recombinant protein Dep44. The adjuvant anti-infective potential of the recombinant protein was subsequently validated in in vitro and vivo experiments.
resultsA K64-specific lytic phage, vB_Kpn_HF1013, was efficiently isolated from hospital wastewater. Dep44 effectively degraded the capsular polysaccharides of K64-CRKP without directly inhibiting bacterial growth. In vivo, Dep44 treatment significantly reduced pulmonary bacterial loads (P < 0.0001), mitigated histopathological lung damage, and suppressed inflammatory cytokine expression (Il6, Il1b). Transcriptomic analysis revealed upregulation of B-cell receptor-related genes and downregulation of proinflammatory pathways, including TNF and JAK-STAT signaling. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed significant downregulation of pathways linked to acute inflammation, tissue injury, and apoptosis.
conclusionDep44 exhibits robust capsule-depolymerizing activity and confers significant protection against K64-CRKP-induced lung infection in mice. These findings highlight its potential as a promising adjunct or alternative to antibiotic therapy for CRKP infections.
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