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Understanding the Impact of Temperate Bacteriophages on Their Lysogens Through Transcriptomics
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Prophage Activation: An In Silico Platform for Identifying Prophage Regulatory Elements to Inform Phage Engineering

Saher Musrrat1,2, Zequan Han3, Kai Wang4

  • 1State Key Laboratory of Quantitative Synthetic Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China

Life (Basel, Switzerland)
|September 27, 2025
PubMed
Summary

Innovative bioinformatics tools identify and engineer transcription factor binding sites (TFBS) to activate bacteriophages for combating multidrug-resistant infections. This approach enhances phage therapy potential and enables personalized treatments against antibiotic resistance.

Keywords:
bacteriophage engineeringlysogenic–lytic switchmultidrug-resistant bacteriaphage therapyregulatory element editing

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Area of Science:

  • Microbiology
  • Bioinformatics
  • Genetics

Background:

  • Multidrug-resistant bacterial infections are a growing global health crisis.
  • Traditional antibiotics are becoming less effective, necessitating novel therapeutic strategies.
  • Phage therapy, using bacteriophages to kill bacteria, shows promise but requires better-characterized phages.

Purpose of the Study:

  • To develop a computational platform for identifying and analyzing transcription factor binding sites (TFBS) in bacteriophages.
  • To engineer TFBS to disrupt host-mediated repression and activate the lytic cycle of prophages.
  • To broaden the spectrum of therapeutic phages and enable individualized phage-based treatments.

Main Methods:

  • Utilized advanced bioinformatics tools to accurately identify and analyze TFBS.
  • Simulated modifications of TFBS to computationally predict reduced repressor activity.
  • Focused on regulatory nodes controlling the transition between lysogenic dormancy and lytic activation.

Main Results:

  • The platform successfully identified and analyzed TFBS.
  • Computational simulations predicted reduced repressor activity upon TFBS modification.
  • Demonstrated the potential for targeted prophage activation and bacterial cell lysis.

Conclusions:

  • The developed methodology offers a novel strategy for engineering therapeutic bacteriophages.
  • Precise identification and engineering of TFBS can overcome limitations in current phage therapy.
  • This approach provides a foundation for developing personalized phage-based therapies against antibiotic-resistant bacteria.