Selective heterogeneity in exoprotease production by Bacillus subtilis

• Published in: PloS one 2012-06, Vol.7 (6), p.e38574-e38574
• Main Authors: Davidson, Fordyce A, Seon-Yi, Chung, Stanley-Wall, Nicola R
• Format: Article
• Language: English
• Subjects: Analysis; Bacillus subtilis; Bacillus subtilis - genetics; Bacillus subtilis - metabolism; Bacteria; Bacterial Proteins - genetics; Bacterial Proteins - metabolism; Biofilms; Biology; Cell differentiation; Cellular manufacture; Chemical reactions; Computer Science; Computer simulation; Differentiation (biology); Environmental changes; Epigenetics; Exopeptidases - genetics; Exopeptidases - metabolism; Gene expression; Gene Expression Regulation, Bacterial; Heterogeneity; Kinases; Mathematical models; Mathematics; Motility; Noise; Phosphorylation; Population; Protease; Proteases; Proteinase; Proteins; Regulators; Signaling; Stochasticity; Transcription Factors - genetics; Transcription Factors - metabolism
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0038574

Bacteria have elaborate signalling mechanisms to ensure a behavioural response that is most likely to enhance survival in a changing environment. It is becoming increasingly apparent that as part of this response, bacteria are capable of cell differentiation and can generate multiple, mutually exclusive co-existing cell states. These cell states are often associated with multicellular processes that bring benefit to the community as a whole but which may be, paradoxically, disadvantageous to an individual subpopulation. How this process of cell differentiation is controlled is intriguing and remains a largely open question. In this paper, we consider an important aspect of cell differentiation that is known to occur in the gram-positive bacterium Bacillus subtilis: we investigate the role of two master regulators DegU and Spo0A in the control of extra-cellular protease production. Recent work in this area focussed the on role of DegU in this process and suggested that transient effects in protein production were the drivers of cell-response heterogeneity. Here, using a combination of mathematical modelling, analysis and stochastic simulations, we provide a complementary analysis of this regulatory system that investigates the roles of both DegU and Spo0A in extra-cellular protease production. In doing so, we present a mechanism for bimodality, or system heterogeneity, without the need for a bistable switch in the underlying regulatory network. Moreover, our analysis leads us to conclude that this heterogeneity is in fact a persistent, stable feature. Our results suggest that system response is divided into three zones: low and high signal levels induce a unimodal or undifferentiated response from the cell population with all cells OFF and ON, respectively for exoprotease production. However, for intermediate levels of signal, a heterogeneous response is predicted with a spread of activity levels, representing typical "bet-hedging" behaviour.