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.
Staphylococcus aureus pathogenicity islands (SaPIs) are molecular parasites that hijack helper phages for their transfer. SaPIbov5, the prototypical member of a family of cos type SaPIs, redirects the assembly of ϕ12 helper capsids from prolate to isometric. This size and shape shift is dependent on the SaPIbov5-encoded protein Ccm, a homolog of the ϕ12 capsid protein (CP). Using cryo-electron microscopy, we have determined structures of prolate ϕ12 procapsids and isometric SaPIbov5 procapsids. ϕ12 procapsids have icosahedral end caps with Tend = 4 architecture and a Tmid = 14 cylindrical midsection, whereas SaPIbov5 procapsids have T = 4 icosahedral architecture. We built atomic models for CP and Ccm, and show that Ccm occupies the pentameric capsomers in the isometric SaPIbov5 procapsids, suggesting that preferential incorporation of Ccm pentamers prevents the cylindrical midsection from forming. Our results highlight that pirate elements have evolved diverse mechanisms to suppress phage multiplication, including the acquisition of phage capsid protein homologs.
Staphylococcus epidermidis is an opportunistic pathogen of the human skin, often associated with infections of implanted medical devices. An increase in antibiotic resistance in S. epidermidis and other bacterial pathogens has led to renewed interest in the use of bacteriophages as an alternative to conventional antibiotics. 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 the capsid and tail proteins, including twelve trimers of a unique receptor binding protein, the hexameric tail knob that acts as a gatekeeper for DNA ejection, and the tail tip, which is a heterooctamer of two different lytic proteins. Our findings elucidate critical features that enable host recognition and penetration, facilitating the development of this group of phages for therapeutic applications.
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