SosA inhibits cell division in Staphylococcus aureus in response to DNA damage

Inhibiting cell division under DNA-damaging conditions is critical for cell viability. In bacterial cells, DNA damage induces the SOS response, which inhibits cell division to prevent compounding damage while repairs are made. In the rod-shaped bacterium, Escherichia coli, the SOS-controlled inhibitor SulA blocks division at an early step, but in coccoid bacteria, such as the human pathogen Staphylococcus aureus, the link between DNA damage and cell-division inhibition remains poorly understood. To enhance our knowledge and provide unique pathways for therapeutic intervention, we studied this process in S. aureus and have identified and characterized an SOS-induced cell-division inhibitor, designated SosA. In contrast to cells lacking sosA, wildtype cells increase in size upon DNA damage due to cell-division inhibition and display a concomitant superior viability. This 77-amino-acid protein is conserved in S. aureus, with homologs being present among staphylococci, and we have provided evidence to support its predicted membrane localization. Functional studies showed that it does not interfere with early cell-division events, such as Z-ring formation, but rather interacts with known divisome components, particularly PBP1, at a later stage. Characterization of truncated SosA variants and mutant strains revealed that the extracellular C-terminus of SosA serves dual functions as a required component for cell-division inhibition while simultaneously controlling SosA levels by acting as a likely target for degradation by the uncharacterized membrane protease CtpA. Our findings provide important insights into the regulation of cell division in coccoid bacteria that in turn may foster development of new classes of antibiotics targeting this essential process.