Spo0A∼P Imposes a Temporal Gate for the Bimodal Expression of Competence in Bacillus subtilis
ComK transcriptionally controls competence for the uptake of transforming DNA in Bacillus subtilis. Only 10%â20% of the cells in a clonal population are randomly selected for competence. Because ComK activates its own promoter, cells exceeding a threshold amount of ComK trigger a positive feedback loop, transitioning to the competence ON state. The transition rate increases to a maximum during the approach to stationary phase and then decreases, with most cells remaining OFF. The average basal rate of comK transcription increases transiently, defining a window of opportunity for transitions and accounting for the heterogeneity of competent populations. We show that as the concentration of the response regulator Spo0A~P increases during the entry to stationary phase it first induces comK promoter activity and then represses it by direct binding. Spo0A~P activates by antagonizing the repressor, Rok. This amplifies an inherent increase in basal level comK promoter activity that takes place during the approach to stationary phase and is a general feature of core promoters, serving to couple the probability of competence transitions to growth rate. Competence transitions are thus regulated by growth rate and temporally controlled by the complex mechanisms that govern the formation of Spo0A~P. On the level of individual cells, the fate-determining noise for competence is intrinsic to the comK promoter. This overall mechanism has been stochastically simulated and shown to be plausible. Thus, a deterministic mechanism modulates an inherently stochastic process. Populations of bacterial cells sometimes bifurcate into subpopulations with different patterns of gene expression. The soil bacterium B. subtilis becomes âcompetentâ for the uptake of environmental DNA, thus acquiring new genetic information. About 15% of the cells are chosen for expression of the competence genes by stochastic fluctuations in the transcription of comK. When the concentration of ComK exceeds a critical threshold, it activates its own expression, a molecular switch is thrown, and competence ensues in that cell. Here we ask why all of the cells do not eventually throw the switch. We show that the basal level expression of comK increases and then decreases as nutrients are exhausted, so that the number of cells exceeding the ComK threshold rises and falls, opening and closing a window of opportunity for competence. Two factors responsible for this âuptickâ in comK expression are: 1) a global increase in transcription as cell division slows, and 2) a continual rise in the concentration of the master regulatory protein Spo0A-P, which activates and then represses comK as it accumulates. The global increase transmits growth rate information and the increase in Spo0A~P encodes multiple signals, including the nutritional, replication, and population density status of the culture.