Isolation and characterization of a lytic phage targeting carbapenem-resistant Pseudomonas aeruginosa.

Carbapenem-resistant Pseudomonas aeruginosa (CRPA) is a major clinical challenge because of the limited availability of effective treatment options. In this study, we isolated four phages, designated Zpj1-Zpj4, from hospital sewage samples using the clinical strain CRPA-11d as the host. Genomic analysis showed that these phages were closely related double-stranded DNA phages and lacked identifiable genes associated with lysogeny, virulence, or antibiotic resistance. Taxonomic analysis assigned them to the genus Yuavirus, subfamily Rabinowitzvirinae, family Mesyanzhinovviridae, and class Caudoviricetes. Among them, phage Zpj4 was selected for further characterization. Its biological properties were evaluated by determining genomic features, optimal multiplicity of infection (MOI), one-step growth kinetics, host range, efficiency of plating (EOP), stability, and in vitro antibacterial and anti-biofilm activities. Its therapeutic efficacy was further assessed in a CRPA-11d induced mouse model of acute lung injury by measuring bacterial burdens in the lungs, livers, and spleens, together with lung histopathology. Phage Zpj4 exhibited favorable properties, including a short latent period, a high burst size, and strong stability. It markedly inhibited CRPA-11d growth and biofilm formation in vitro. In the mouse model, phage Zpj4 treatment significantly reduced bacterial burdens in the lungs, livers, and spleens and alleviated lung tissue injury. These findings indicated that phage Zpj4 is a promising candidate for the treatment of CRPA infections.