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Published on: January 8, 2020
Isolation and characterization of a lytic phage targeting carbapenem-resistant Pseudomonas aeruginosa
Panhong Jia1, Xiangqin Wang2, Yi Jian3
1Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530021, China; Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou, Zhejiang, 325000, China; Department of Respiratory and Critical Care Medicine, The People's Hospital of Beihai, Beihai, Guangxi, 536000, China.
Abstract:
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.
Insights
Phage Zpj4 effectively targets carbapenem-resistant Pseudomonas aeruginosa (CRPA), a difficult-to-treat infection. This bacteriophage demonstrated significant antibacterial and anti-biofilm activity in vitro and reduced bacterial load and lung injury in a mouse model.
Area of Science:
- Microbiology
- Virology
- Infectious Diseases
Background:
- Carbapenem-resistant Pseudomonas aeruginosa (CRPA) presents a significant clinical challenge due to limited effective treatments.
- Bacteriophage therapy offers a potential alternative for combating multidrug-resistant bacterial infections.
Purpose of the Study:
- To isolate and characterize bacteriophages effective against CRPA.
- To evaluate the therapeutic potential of a selected phage (Zpj4) in vitro and in a preclinical mouse model.
Main Methods:
- Isolation of four phages (Zpj1-Zpj4) from hospital sewage using CRPA as the host.
- Genomic and taxonomic analysis of isolated phages.
- In vitro characterization of phage Zpj4, including stability, host range, and antibacterial/anti-biofilm activity.
- In vivo efficacy assessment in a CRPA-induced acute lung injury mouse model.
Main Results:
- Phages Zpj1-Zpj4 were identified as double-stranded DNA viruses belonging to the Yuavirus genus, lacking virulence or resistance genes.
- Phage Zpj4 displayed favorable biological properties, including high stability and potent in vitro inhibition of CRPA growth and biofilm formation.
- In the mouse model, Zpj4 treatment significantly reduced bacterial burdens in multiple organs and ameliorated lung histopathology.
Conclusions:
- Phage Zpj4 exhibits promising therapeutic potential against CRPA infections.
- Further development of Zpj4 as a phage therapy agent is warranted for clinical application.
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