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Phage Phenomics: Physiological Approaches to Characterize Novel Viral Proteins
Published on: June 11, 2015
Cross-genus phage design through branching domain and conserved peptide interactions
Agnieszka Latka1,2, Dorien Dams1, Lennert Scholiers1
1Department of Biotechnology, Ghent University, Valentin Vaerwyckweg 1, Gent, 9000, Belgium.
Journal of Biological Engineering
|May 19, 2026
Summary
Researchers engineered bacteriophages to infect new hosts by understanding how receptor-binding proteins (RBPs) interact. This modular approach allows for customized therapeutic phages with broader host ranges, including cross-genus infections.
Area of Science:
- Microbiology
- Molecular Biology
- Biotechnology
Background:
- Bacteriophage host range is often limited by receptor-binding proteins (RBPs).
- Branched RBP systems with multiple RBPs can broaden phage infectivity.
- The interaction between RBP1 and RBP2 is crucial for dual-RBP incorporation.
Purpose of the Study:
- To investigate the interaction between RBP domains for dual-RBP incorporation.
- To engineer bacteriophages with expanded host ranges using modular RBP engineering.
- To establish a mechanistic framework for rational phage engineering.
Main Methods:
- Experimental validation of RBP1 branching domain and RBP2 docking peptide interaction.
- Systematic engineering of RBP domains to study their role in assembly.
- Chimeric phage construction through modular domain swapping and RBP positional relocation.
Main Results:
- Loss of RBP branching domain or conserved peptide abolishes RBP2 assembly.
- The anchor domain is the sole element attaching the RBP complex to the virion.
- Engineered chimeric phages achieved cross-genus infection (Klebsiella and Escherichia) and productive propagation.
Conclusions:
- RBP branching domain and conserved peptide are specific interacting partners.
- The conserved peptide acts as a docking element for RBP assembly.
- Podovirus structural flexibility allows accommodation of RBPs from different contexts, enabling rational phage engineering for expanded host spectrum.
Keywords:
Branching domainConserved peptideDepolymeraseHost rangeKlebsiella phageReceptor-binding proteinTailspikeMore Related Videos
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