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Related Concept Videos

Lytic Cycle of Bacteriophages01:30

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Bacteriophages, also known as phages, are specialized viruses that infect bacteria. A key characteristic of phages is their distinctive “head-tail” morphology. A phage begins the infection process (i.e., lytic cycle) by attaching to the outside of a bacterial cell. Attachment is accomplished via proteins in the phage tail that bind to specific receptor proteins on the outer surface of the bacterium. The tail injects the phage’s DNA genome into the bacterial cytoplasm. In the...
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In contrast to the lytic cycle, phages infecting bacteria via the lysogenic cycle do not immediately kill their host cell. Instead, they combine their genome with the host genome, allowing the bacteria to replicate the phage DNA along with the bacterial genome. The incorporated copy of the phage genome is called the prophage. Some prophages can re-activate and enter the lytic cycle. This often occurs in response to a perturbation, such as DNA damage, but can also transpire in the absence of...
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Programming virulent bacteriophages by developing a multiplex genome engineering method.

Hailin Zhang1,2, Ru Zhu1, Zhaofei Wang3

  • 1State Key Laboratory of Microbial Technology, Institute of Microbial Technology, Helmholtz International Lab for Anti-infectives, Shandong University-Helmholtz Institute of Biotechnology, Shandong University, Qingdao, Shandong, China.

Mbio
|May 23, 2025
PubMed
Summary
This summary is machine-generated.

We developed a SMART method for engineering virulent bacteriophages (phages). This technique enables multiplex genome modification, creating custom phages to combat bacterial infections effectively.

Keywords:
genome engineeringphage chassisphage engineeringrecombineeringsynthetic phages

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Area of Science:

  • Synthetic biology
  • Microbiology
  • Genetics

Background:

  • Virulent bacteriophages (phages) show promise for combating pathogenic bacteria.
  • Engineering virulent phage genomes is challenging due to rapid lysis and toxic gene products.

Purpose of the Study:

  • To develop a method for multiplex genome engineering of virulent phages.
  • To create a chassis phage and synthetic phages with enhanced lytic capabilities.

Main Methods:

  • Developed the SMART (splitting, modifying, assembling, and rebooting) method.
  • Engineered the T7 E. coli phage genome by splitting, modifying, assembling, and rebooting.
  • Constructed synthetic T7 phages expressing heterologous lysins.

Main Results:

  • Successfully deleted 3.9 kb across 8 sites in the T7 phage genome, creating a chassis phage.
  • Demonstrated the insertion capacity and expression of exogenous genes in the chassis phage.
  • Engineered synthetic T7 phages that efficiently lyse E. coli, S. aureus, and S. agalactiae.

Conclusions:

  • The SMART method facilitates multiplex genome engineering of virulent phages.
  • Custom-designed phages can be created for therapeutic applications with enhanced efficacy and specificity.