Deciding fate in adverse times: Sporulation and competence in Bacillus subtilis

Abstract

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.

Bacteria determine fate by playing dice with controlled odds

“…The core of the matter is the difference in the stochastic behaviors of the transcription factors' (TFs) binding and unbinding events. Whereas binding reactions depend on the concentration of transcription factors, the unbinding reactions are concentration independent (6,11,13,14). Therefore, the two circuits give rise to different noise behaviors in the "on" and "off" states of A.…”

“…In some parts of the network, noise is undesirable, such as in the commitment to sporulation. Fluctuations leading to a decision to sporulate at inconvenient times could have devastating consequences to the colony; therefore, the system has evolved to integrate stress signals over time, filtering out transient activations and guaranteeing a robust response (11). In other parts of the network, however, noise can be amplified by gene circuits with special architecture, such as the AbrB circuit discussed further below (11).…”

“…Specialized gene circuits have evolved to coordinate the decision-making between different individual cells, such as the quorum sensing and the Rap systems which control sporulation and competence transitions (11). One fascinating example is the AbrB decision-making circuit shown in Fig.…”

“…One fascinating example is the AbrB decision-making circuit shown in Fig. 2, which has a surprising dual role as noise amplifier and cell-cell coordinator (11). The existence of many sophisticated circuits that incorporate cell-cell communication in the fate decisions of individual cells might suggest metaevolution of decision-making and communication circuits architecture, noise, and function.…”

“…These observations imply that stochastic cell differentiations are carried out with controlled odds to fit the needs of the population as a whole. Cellular capacity to manage the odds entails means to program and regulate the noise level and means to program the effect of the noise on the gene circuit performance (4)(5)(6)(7)(8)(9)11). Several studies show that circuit architecture can encode distinct noise behaviors critical for circuit task performance (3-5, 12, 13).…”