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Coevolutionary phage training expands phage host range: Driven by tail fiber mutations in Pseudomonas aeruginosa

Zixun Lin1, Xiangke Duan2, Xiaofu Wan2

  • 1National Clinical Research Center for Infectious Diseases, The Third People's Hospital of Shenzhen and The Second Affiliated Hospital of Southern University of Science and Technology, Shenzhen, Guangdong, China; School of Medicine, Southern University of Science and Technology, Shenzhen, Guangdong, China.

Microbiological Research
|August 26, 2025
PubMed

Insights

Bacteriophages (viruses that infect bacteria) were evolved to broaden their attack range against multidrug-resistant Pseudomonas aeruginosa. This enhanced phage therapy offers a new strategy to combat dangerous bacterial infections.

Area of Science:

  • Microbiology
  • Genetics
  • Biotechnology

Background:

  • Antibiotic-resistant bacteria, like Pseudomonas aeruginosa, pose a significant global health threat.
  • Bacteriophage therapy is a promising alternative to antibiotics but is limited by narrow host specificity.

Purpose of the Study:

  • To engineer the host range of Pseudomonas aeruginosa phage pap17.
  • To develop an evolutionary strategy for enhancing phage efficacy against resistant bacterial strains.

Main Methods:

  • Experimental evolution involving co-culturing phage pap17 with permissive and non-permissive Pseudomonas aeruginosa strains.
  • Genomic analysis to identify mutations responsible for host range expansion.
  • Assessment of evolved phages' stability and lytic activity.

Main Results:

  • Evolved pap17 phages acquired the ability to infect previously non-permissive strains.
  • Infectivity against original hosts was maintained.
  • Key mutations were identified in the phage's tail fiber protein.
  • Evolved phages showed improved stability and lytic activity.

Conclusions:

  • Experimental evolution can successfully broaden bacteriophage host range.
  • Engineered phages demonstrate potential for combating multidrug-resistant Pseudomonas aeruginosa.
  • This approach offers a viable strategy to enhance phage therapy effectiveness.
Keywords:
Host range expansionPhagePhage resistancePseudomonas aeruginosaTail fiber protein

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