The transcription factor DksA exerts opposing effects on cell division depending on the presence of ppGpp.

Cell division is a key step in the bacterial lifecycle that must be appropriately regulated to ensure survival. This work identifies the alarmone ppGpp as a general regulator of cell division, extending our understanding of the role of ppGpp beyond a signal for starvation and other stress. Even in nutrient replete conditions, basal levels of ppGpp are essential for division to occur appropriately and for cell size to be maintained. This study establishes ppGpp as a "switch" that controls whether the transcription factor DksA behaves as a division activator or inhibitor. This unexpected finding enhances our understanding of the complex regulatory mechanisms employed by bacteria to coordinate division with diverse aspects of cell growth and stress response. Because division is an essential process, a better understanding the mechanisms governing assembly and activation of the division machinery could contribute to the development of novel therapeutics to treat bacterial infections.