Structure and genome ejection mechanism of Podoviridae phage P68 infecting Staphylococcus aureus

Phages infecting S. aureus have the potential to be used as therapeutics against antibiotic-resistant bacterial infections. However, there is limited information about the mechanism of genome delivery of phages that infect Gram-positive bacteria. Here we present the structures of S. aureus phage P68 in its native form, genome ejection intermediate, and empty particle. The P68 head contains seventy-two subunits of inner core protein, fifteen of which bind to and alter the structure of adjacent major capsid proteins and thus specify attachment sites for head fibers. Unlike in the previously studied phages, the head fibers of P68 enable its virion to position itself at the cell surface for genome delivery. P68 genome ejection is triggered by disruption of the interaction of one of the portal protein subunits with phage DNA. The inner core proteins are released together with the DNA and enable the translocation of phage genome across the bacterial membrane into the cytoplasm.