Deciding fate in adverse times: sporulation and competence in Bacillus subtilis.

Bacteria serve as the central arena for understanding how gene networks and proteins process information and control cellular behaviors. Recently, much effort has been devoted to the investigation of specific bacteria gene circuits as functioning modules. The next challenge is the integrative modeling of complex cellular networks composed of many such modules. A tractable integrative model of the sophisticated decision-making signal transduction system that determines the fate between sporulation and competence is presented. This model provides an understanding of how information is sensed and processed to reach an "informative" decision in the context of cell state and signals from other cells. The competence module (ComK dynamics) is modeled as a stochastic switch whose transition rate is controlled by a quorum-sensing unit. The sporulation module (Spo0A dynamics) is modeled as a timer whose clock rate is adjusted by a stress-sensing unit. The interplay between these modules is mediated via the Rap assessment system, which gates the sensing units, and the AbrB-Rok decision module, which creates an opportunity for competence within a specific window of the sporulation timer. The timer is regulated via a special repressilator-like inhibition of Spo0A* by Spo0E, which is itself inhibited by AbrB. For some stress and input signals, this repressilator can generate a frustration state with large variations (fluctuations or oscillations) in Spo0A* and AbrB concentrations, which might serve an important role in generating cell variability. This integrative framework is a starting point that can be extended to include transition into cannibalism and the role of colony organization.