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Published on: June 28, 2024
Structure and host specificity of Staphylococcus epidermidis bacteriophage Andhra
N'Toia C Hawkins1, James L Kizziah1, Asma Hatoum-Aslan2
1Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Abstract:
Staphylococcus epidermidis is an opportunistic pathogen of the human skin, often associated with infections of implanted medical devices. Staphylococcal picoviruses are a group of strictly lytic, short-tailed bacteriophages with compact genomes that are attractive candidates for therapeutic use. Here, we report the structure of the complete virion of S. epidermidis-infecting phage Andhra, determined using high-resolution cryo-electron microscopy, allowing atomic modeling of 11 capsid and tail proteins. The capsid is a T = 4 icosahedron containing a unique stabilizing capsid lining protein. The tail includes 12 trimers of a unique receptor binding protein (RBP), a lytic protein that also serves to anchor the RBPs to the tail stem, and a hexameric tail knob that acts as a gatekeeper for DNA ejection. Using structure prediction with AlphaFold, we identified the two proteins that comprise the tail tip heterooctamer. Our findings elucidate critical features for virion assembly, host recognition, and penetration.
Insights
Researchers determined the structure of the Staphylococcus epidermidis-infecting phage Andhra using cryo-electron microscopy. This reveals key features of the bacteriophage
Area of Science:
- Structural Biology
- Microbiology
- Virology
Background:
- Staphylococcus epidermidis is a skin pathogen linked to medical device infections.
- Staphylococcal picoviruses are lytic bacteriophages with therapeutic potential.
Purpose of the Study:
- To determine the complete virion structure of S. epidermidis-infecting phage Andhra.
- To enable atomic modeling of capsid and tail proteins for understanding phage assembly and function.
Main Methods:
- High-resolution cryo-electron microscopy (cryo-EM) for complete virion structure determination.
- Atomic modeling of 11 capsid and tail proteins.
- AlphaFold structure prediction for tail tip heterooctamer identification.
Main Results:
- The capsid is a T=4 icosahedron with a unique stabilizing inner lining protein.
- The tail comprises receptor binding proteins (RBPs), a lytic protein, and a DNA ejection gatekeeper tail knob.
- The tail tip heterooctamer composition was identified using AlphaFold.
Conclusions:
- The determined structure elucidates critical features for phage assembly.
- Understanding these features is vital for host recognition and penetration mechanisms.
- This research provides insights into bacteriophage structure for potential therapeutic applications.
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