Stochastic antagonism between two proteins governs a bacterial cell fate switch


Lord, N. D. ; Norman, T. M. ; Yuan, R. ; Bakshi, S. ; Losick, R. ; Paulsson, J. Stochastic antagonism between two proteins governs a bacterial cell fate switch. Science 2019, 366, 116–120.


Cell survival can require switching mechanisms that are flexible enough to accommodate environmental changes but also stable for the required duration. Lord et al. created a switching system in bacteria based on stochastic competition between two proteins: one is a transcriptional repressor, and the other is an antagonist that binds the repressor and locks it in an inactive state. They show that this system controls switching of the bacterium Bacillus subtilis from a motile, unicellular state to an immobile, multicellular state, and that the control system is transferable to another distantly related bacterium. Similar mechanisms could be more widely operable in biological systems than previously recognized.Science, this issue p. 116Cell fate decision circuits must be variable enough for genetically identical cells to adopt a multitude of fates, yet ensure that these states are distinct, stably maintained, and coordinated with neighboring cells. A long-standing view is that this is achieved by regulatory networks involving self-stabilizing feedback loops that convert small differences into long-lived cell types. We combined regulatory mutants and in vivo reconstitution with theory for stochastic processes to show that the marquee features of a cell fate switch in Bacillus subtilis—discrete states, multigenerational inheritance, and timing of commitments—can instead be explained by simple stochastic competition between two constitutively produced proteins that form an inactive complex. Such antagonistic interactions are commonplace in cells and could provide powerful mechanisms for cell fate determination more broadly.