A mechanical model for the coordination of septum formation and cell splitting in Staphylococcus aureus

Staphylococcus aureus divides by building an internal septum followed by rapid cell splitting. These are usually thought of as separate processes, with splitting occuring after septum formation is complete. Cell splitting is known to involve both mechanical forces and peptidoglycan (PG) hydrolase activity, but the coordination between PG mechanics and hydrolase activity is poorly understood. Here, we propose a theoretical model that connects PG mechanics and hydrolase activity and predicts the coordinated timing of septum formation and cell splitting. We calculate using a thin-shell mechanical model the dynamical pattern of local stress in the cell wall during the S. aureus cell cycle, finding that the onset of septum formation decreases the stress close to the midplane. We hypothesize that hydrolase activity is triggered by the local decrease in stress, leading to cell splitting. In our model, the timing of septum completion and cell splitting depends on the relative rates of PG synthesis and hydrolysis as well as cell size, PG thickness and stiffness, and turgor pressure. Our model can explain different cell division defects including premature splitting before septum formation is complete, and failure to initiate splitting. The model can also predict quantiatively changes in the timing of the later phases of the cell cycle among several S. aureus mutants and in the presence of the antibiotic methicillin, using parameters from atomic force microscopy. Our predictions are tested against microscopy data.