Agent-based modeling of competence phenotype switching in Bacillus subtilis
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RESEARCH
Open Access
Agent-based modeling of competence phenotype switching in Bacillus subtilis Suzy M Stiegelmeyer1* and Morgan C Giddings2,3,4 * Correspondence: [email protected] 1 Syngenta Biotechnology, Inc., 3054 Cornwallis Rd,, Research Triangle Park, NC 27709, USA Full list of author information is available at the end of the article
Abstract Background: It is a fascinating phenomenon that in genetically identical bacteria populations of Bacillus subtilis, a distinct DNA uptake phenotype called the competence phenotype may emerge in 10–20% of the population. Many aspects of the phenomenon are believed to be due to the variable expression of critical genes: a stochastic occurrence termed “noise” which has made the phenomenon difficult to examine directly by lab experimentation. Methods: To capture and model noise in this system and further understand the emergence of competence both at the intracellular and culture levels in B. subtilis, we developed a novel multi-scale, agent-based model. At the intracellular level, our model recreates the regulatory network involved in the competence phenotype. At the culture level, we simulated growth conditions, with our multi-scale model providing feedback between the two levels. Results: Our model predicted three potential sources of genetic “noise”. First, the random spatial arrangement of molecules may influence the manifestation of the competence phenotype. In addition, the evidence suggests that there may be a type of epigenetic heritability to the emergence of competence, influenced by the molecular concentrations of key competence molecules inherited through cell division. Finally, the emergence of competence during the stationary phase may in part be due to the dilution effect of cell division upon protein concentrations. Conclusions: The competence phenotype was easily translated into an agent-based model – one with the ability to illuminate complex cell behavior. Models such as the one described in this paper can simulate cell behavior that is otherwise unobservable in vivo, highlighting their potential usefulness as research tools. Keywords: Agent-based modeling, Bacillus subtilis, Bistable switch, Competence
Background The competence state exhibited by Bacillus subtilis is an example of a bacterial phenotype driven by changes in gene and protein expression states rather than changes in genotype [1]. Competence is a DNA uptake mechanism that appears to be a cell survival strategy for either procuring new genetic information or obtaining DNA as food. The emergence of competence is correlated with high cell density and nutrient limiting conditions [1]. In those conditions, approximately 10–20% of a B. subtilis population will express the competence phenotype [1]. The mechanism by which a small fraction of the population becomes competent is presently attributed to the variable expression © 2013 Stiegelmeyer and Giddings; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http
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