Abstract
BackgroundQuorum sensing drives biofilm formation in bacteria in order to ensure that biofilm formation only occurs when colonies are of a sufficient size and density. This spatial behaviour is achieved by the broadcast communication of an autoinducer in a diffusion scenario. This is of interest, for example, when considering the role of gut microbiota in gut health. This behaviour occurs within the context of the four phases of bacterial growth, specifically in the exponential stage (phase 2) for autoinducer production and the stationary stage (phase 3) for biofilm formation.ResultsWe have used coloured hybrid Petri nets to step-wise develop a flexible computational model for E.coli biofilm formation driven by Autoinducer 2 (AI-2) which is easy to configure for different notions of space. The model describes the essential components of gene transcription, signal transduction, extra and intra cellular transport, as well as the two-phase nature of the system. We build on a previously published non-spatial stochastic Petri net model of AI-2 production, keeping the assumptions of a limited nutritional environment, and our spatial hybrid Petri net model of biofilm formation, first presented at the NETTAB 2017 workshop. First we consider the two models separately without space, and then combined, and finally we add space. We describe in detail our step-wise model development and validation.Our simulation results support the expected behaviour that biofilm formation is increased in areas of higher bacterial colony size and density. Our analysis techniques include behaviour checking based on linear time temporal logic.ConclusionsThe advantages of our modelling and analysis approach are the description of quorum sensing and associated biofilm formation over two phases of bacterial growth, taking into account bacterial spatial distribution using a flexible and easy to maintain computational model. All computational results are reproducible.
Highlights
Quorum sensing drives biofilm formation in bacteria in order to ensure that biofilm formation only occurs when colonies are of a sufficient size and density
We describe in detail our step-wise model development and validation strategy
The spatial model which we have developed and presented in this paper describes E.coli biofilm formation driven by the Autoinducer 2 (AI-2)
Summary
Quorum sensing drives biofilm formation in bacteria in order to ensure that biofilm formation only occurs when colonies are of a sufficient size and density. This spatial behaviour is achieved by the broadcast communication of an autoinducer in a diffusion scenario. This is of interest, for example, when considering the role of gut microbiota in gut health. The human body hosts a large number of prokaryotic and unicellular eukaryotic cells, which are found in most tissues. Gut microbiota have a direct effect on the diseases related to intestines such as Irritable Bowel Syndrome (IBS), Inflammatory Bowel Disease (IBD) [2], metabolic diseases and obesity [4]
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