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.

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.