Cell attachment and tail contraction of S. aureus phage phi812

Phages with contractile tails employ elaborate strategies to penetrate bacterial cell walls and deliver their genomes into the host cytoplasm. Most tailed phages that have been structurally characterized to date infect Gram-negative bacteria, but those targeting Gram-positive bacteria, many of which are important human pathogens, are less well understood. Here, we show that the baseplate of phage phi812, which infects Gram-negative Staphylococcus aureus, is formed of a core, wedge modules, and baseplate arms carrying receptor-binding proteins type 1 and 2 and tripod complexes. Upon binding to the S. aureus cell wall, the symmetry of the baseplate transforms from threefold to sixfold. The conformational changes propagate from the outer edge to the core of the baseplate. The receptor-binding proteins re-orient to bind to the host cell. Subsequently, central spike proteins degrade wall teichoic acid. The conformational changes to the tripod complexes trigger the release of the central spike and weld proteins from the baseplate, which enables the hub proteins to cleave cell wall peptidoglycan and facilitate penetration of the tail tube tip through the cell membrane. Changes in the positions of baseplate arms are transmitted through wedge modules to tail sheath initiator proteins. The ring formed by the tail sheath initiator proteins expands in diameter and thus triggers the contraction of the tail sheath. The tail sheath of phi812, which can bend up to 90° in its native conformation, shortens from ~200 to ~96 nm, which pushes the tip of the tail tube 10-30 nm into the cytoplasm, depending on the local thickness of the S. aureus cell wall. Our results provide the foundation for engineering phi812 to target specific S. aureus strains.