Bacteria can undergo sporulation or competence (the ability to uptake DNA) in response to nutrient deprivation. Süel et al. monitored, in individual Bacillus subtilis cells, the expression of genes in the core signaling circuit that governs competence and analyzed the expression patterns using a mathematical model of a dynamical system that exhibits excitability (that is, small perturbations cause large changes, which eventually return to baseline). The transcription factor ComK is the master regulator of competence, and it stimulates transcription of multiple genes, including its own gene comK and the comG operon. Süel et al. define a core regulatory module "MecKS" for competence in terms of ComK, the MecA complex that degrades ComK, and ComS, which inhibits the MecA complex. They monitored activity of the promoters for the comK and comG genes (PcomK and PcomG) in single cells and also monitored sporulation or competence in the same cells. The activity of the PcomK and PcomG increased at the initiation of competence and declined as cells exited the competent state and returned to vegetative growth. When PcomG and PcomS were monitored simultaneously, the two promoters had an inverse relationship. In competent cells, PcomG increased and PcomS decreased, whereas when cells resumed vegetative growth, activity of PcomG decreased and that of PcomS increased. Using the dynamical model of the MeKS module (which incorporates noise and the positive feedback loop from ComK to itself and the negative feedback loop by which ComK inhibits ComS) to analyze the data, the authors showed that noise-triggered changes in the abundance of ComK or ComS can trigger a large change in what is called the "phase space," which reflects the ability of noise to trigger an increase in ComK and the decrease in ComS associated with acquisition of competence. The model also predicted that interference with the ComS negative feedback should produce a stable system such that the cells cannot exit from competence. The authors produced such a strain and proved this to be correct. The cells in which ComS did not decrease became competent with wild-type frequencies but failed to return to the vegetative state and ultimately died.
G. M. Süel, J. Garcia-Ojalvo, L. M. Liberman, M. B. Elowitz, An excitable gene regulatory circuit induces transient cellular differentiation. Nature 440, 545-550 (2006). [PubMed]