Abstract
The Type III secretion system (TTSS) is a protein secretion machinery used by certain gram-negative bacterial pathogens of plants and animals to deliver effector molecules to the host and is at the core of the ability to cause disease. Extensive molecular and biochemical study has revealed the components and their interactions within this system but reductive approaches do not consider the dynamical properties of the system as a whole. In order to gain a better understanding of these dynamical behaviours and to create a basis for the refinement of the experimentally derived knowledge we created a Boolean model of the regulatory interactions within the hrp regulon of Pseudomonas syringae pathovar tomato strain DC3000 Pseudomonas syringae. We compared simulations of the model with experimental data and found them to be largely in accordance, though the hrpV node shows some differences in state changes to that expected. Our simulations also revealed interesting dynamical properties not previously predicted. The model predicts that the hrp regulon is a biologically stable two-state system, with each of the stable states being strongly attractive, a feature indicative of selection for a tightly regulated and responsive system. The model predicts that the state of the GacS/GacA node confers control, a prediction that is consistent with experimental observations that the protein has a role as master regulator. Simulated gene “knock out” experiments with the model predict that HrpL is a central information processing point within the network.
Highlights
Many gram-negative bacterial pathogens of plants use the Type III Secretion system (TTSS) to deliver effector molecules directly into the host [1]
The TTSS is encoded by around 20 hrp genes that are found in several operons on the chromosome or plasmids of plant-pathogenic bacteria [4]
There is a paucity of kinetic and quantitative information on biochemical parameters such as protein DNA binding affinities, RNA polymerase extension rates and so on in the specific hrp regulon literature, so it is not possible to create detailed continuous or stochastic models without making gross and probably erroneous estimations about the values of these parameters
Summary
Many gram-negative bacterial pathogens of plants use the Type III Secretion system (TTSS) to deliver effector molecules directly into the host [1]. We wanted to know whether a Boolean model could be used to reliably reproduce the observed patterns of expression of the genes of the hrp regulon and if it could be used to identify any interesting dynamical properties of the system that were not obvious from the literature.
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