Cell wall mechanical stress could coordinate septal synthesis and scission in <i>Staphylococcus aureus</i>

<i>Staphylococcus aureus</i> divides by building a septum and then splitting into two daughter cells. Scission should be coordinated with septum completion to avoid cell lysis; however, it is not known how this is achieved, or what the relative roles of mechanical forces and the activity of peptidoglycan hydrolase enzymes are. Here, we show using thin-shell mechanics that septum formation causes a localized decrease in mechanical stress at the cell's equator. We propose that this local decrease in stress could act as a mechanical trigger for hydrolase activity, leading eventually to splitting. This mechanical trigger model can explain observed cell division defects, including premature splitting and failure to initiate splitting. The model also shows how cell size, turgor pressure, cell wall thickness and stiffness, and the relative rates of synthesis and hydrolysis combine to determine cell cycle timing and the outcome of antibiotic exposure. Bacterial cell division requires dynamic orchestration of molecular players, in concert with cell wall mechanics. Our work suggests how mechanical forces could coordinate with enzyme activity in the control of this complex process.IMPORTANCE<i>Staphylococcus aureus</i> is a major threat due to its ability to generate antibiotic-resistant strains. Understanding <i>S. aureus</i> division is therefore of great importance, but we do not know how septum formation is coordinated with cell scission. Previous works have shown that both mechanical stress and autolysin activity play key roles in scission, but it is unclear how mechanical and biochemical cues work together. Here, we propose a "mechanical trigger" model for the interplay between mechanical stress and autolysin activation. We use mathematical modeling to show that stress decreases in the <i>S. aureus</i> cell wall close to the division site as the septum is formed, and we propose that this could trigger autolysin activity. Our model explains reports of diverse division outcomes in the presence of mutations and antibiotics and points to a general link between cell geometry and antibiotic resistance.