Inhibition of peptidoglycan synthesis is sufficient for total arrest of staphylococcal cell division

Bacterial cell wall biosynthesis is the target of many important antibiotics. Its spatiotemporal organization is closely coordinated with cell division. However, the role of peptidoglycan synthesis within cell division is not fully understood. Even less is known about the impact of antibiotics on the coordination of these two essential processes. Visualizing the essential cell division protein FtsZ and other key proteins in Staphylococcus aureus, we show that antibiotics targeting peptidoglycan synthesis arrest cell division within minutes of treatment. The glycopeptides vancomycin and telavancin completely inhibit septum constriction in all phases of cell division. The beta-lactam oxacillin stops division progress by preventing recruitment of the major peptidoglycan synthase PBP2 to the septum, revealing PBP2 as crucial for septum closure. Our work identifies cell division as key cellular target of these antibiotics and provides evidence that peptidoglycan synthesis is the essential driving force of septum constriction throughout cell division of S. aureus.