Systems analysis of a quorum sensing network: Design constraints imposed by the functional requirements, network topology and kinetic constants

Goryachev, Andrew B.; Toh, Da Jun; Lee, T.

doi:10.1016/j.biosystems.2005.04.006

Cited by 84 publications

(95 citation statements)

References 35 publications

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“…An inherent feature of many quorum-sensing systems is the positive-feedback regulatory circuit at the level of autoinducer signal synthesis, which is thought to be a key factor in the switchlike control of quorum-sensing-regulated phenotypes (11)(12)(13)(14)29). However, in P. stewartii subsp.…”

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confidence: 99%

The rcsA Promoter of Pantoea stewartii subsp. stewartii Features a Low-Level Constitutive Promoter and an EsaR Quorum-Sensing-Regulated Promoter

Carlier

Bodman

2006

J Bacteriol

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The upstream region of the Pantoea stewartii rcsA gene features two promoters, one for constitutive basallevel expression and a second autoregulated promoter for induced expression. The EsaR quorum-sensing repressor binds to a site centered between the two promoters, blocking transcription elongation from the regulated promoter under noninducing conditions. Pantoea stewartii subsp. stewartii is the etiological agent of Stewart's wilt disease in maize (2, 3). The organism grows in the plant xylem, where it produces large amounts of stewartan capsular polysaccharide/exopolysaccharide (EPS), thereby impeding normal vascular transport (16). A cluster of 12 genes, designated cps, encodes the functions required for stewartan biosynthesis and translocation (5,8). This gene system is related to group 1 cps gene clusters based on the chromosomal linkage to the rfb and his locus and regulation by the RcsC/ YojN/RcsA/B phosphorelay signal transduction system (17,24,32). The RcsAB heterodimeric transcription factor binds to an RcsAB box element generally located some distance (ϳ100 bp) from the regulated promoters (31).In P. stewartii subsp. stewartii, the synthesis of stewartan EPS is cell density dependent and governed by the EsaI/EsaR quorum-sensing system (28). The EsaI protein is an acyl homoserine lactone (AHL) signal synthase (27,30), and EsaR is the cognate AHL-responsive transcription factor (19,28). This system differs from the LuxR paradigm in that EsaR dimerizes and binds DNA in the absence of the AHL coinducer, thereby repressing or activating target genes depending on the location of the esaR box DNA binding site (18,21,26). We recently reported that EsaR controls the expression of the cps gene system indirectly through transcriptional repression and AHLmediated derepression of the rcsA gene (18). Quorum-sensing systems govern the synthesis of EPS in other phytopathogenic bacteria, but the underlying regulatory mechanisms differ (7, 9, 22). To our knowledge, P. stewartii subsp. stewartii represents the only described example of a species in which the rcsA gene is under direct quorum-sensing control (18).In this study, we identify the transcriptional start site(s) and promoter site(s) within the upstream region of the rcsA gene to further define the mode of quorum-sensing regulation at this promoter. We observe that the rcsA gene expresses at significant basal levels from a previously unrecognized constitutive promoter and that the induced expression initiates from a separate, AHL-inducible, RcsA-autoregulated promoter. The previously established EsaR DNA binding site (18, 19) is centered between the two promoters, suggesting that EsaR represses transcription by interfering with transcription elongation rather than by steric exclusion of RNA polymerase from the inducible promoter.Bacterial strains and growth conditions. The P. stewartii subsp. stewartii strains used in this study were ESN10 and ESN51, which are mutant strains derived from the wild-type strain DC283 (8). These strains carry different mutated all...

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confidence: 99%

The rcsA Promoter of Pantoea stewartii subsp. stewartii Features a Low-Level Constitutive Promoter and an EsaR Quorum-Sensing-Regulated Promoter

Carlier

Bodman

2006

J Bacteriol

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“…Figure 3B shows the distribution of the average pathway lengths. Again, the distribution for all node pairs and the non-perturbation group peaks at the same average length (8), but for the perturbation group, the peak is located at a smaller length (6). Additionally, more node pairs have small average lengths (1-4) in the perturbation group than in the non-perturbation group.…”

Section: Tail/perturbeementioning

confidence: 91%

“…Kuo et al 5 studied the network topology and the evolution of dynamics in an artificial genetic regulatory network model. Using an in silico perturbation approach, Goryachev et al 6 identified an auxiliary positive feedback loop together with dimerization of the transcription factor, which is important to the switch-like behavior of the network. In these works, mathematical modeling and in silico simulation proved to be very useful in revealing the hidden structure-function relationship in the network.…”

Section: Introductionmentioning

confidence: 99%

Network Robustness Due to Multiple Positive Feedback Loops: A Systematic Study of a Th Cell Differentiation Model

Gong

Zhang

B??R??³

2010

Signal Transduction Insights

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Positive feedback loops have been identified in many biological signal transduction systems. Their importance in a system's bistability has been well established by identifying multiple steady states of a network under different parameters. In this paper, we identify the contribution of positive feedback loops to network robustness by a systematic comparison between network structures and responses to perturbations at a pre-steady state. Our study is based on a T helper (Th) cell differentiation model in which positive feedback loops give rise to a subnet robustness against both positive and negative perturbations from outside the subnet. Although it is unclear whether this pre-steady state exists in vivo, the results from in silico modeling are in agreement with the reported in vivo observations. Being highly heterogeneous and rarely at a steady state, the disease cells, such as cancer cells, may gain potential resistances to certain drugs in a similar way. From the reverse engineering point of view, our results confirm that, while data from perturbation experiments are very effective in identifying causal relationships among the network components, caution should be taken, as in some circumstances, a direct interaction could be invisible due to positive feedback loops.

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“…We neglect possible feedbacks (cf. [13,20]) on the transcription of PpuR, as these seem to be of minor influence [16]. Thus, just a constant basic production of the receptor PpuR is considered, as in [10,11,17].…”

Section: Regulatory Pathway In One Cellmentioning

confidence: 99%

Mathematical Modeling of Bacteria Communication in Continuous Cultures

Barbarossa

Kuttler²

2016

Applied Sciences

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Quorum sensing is a bacterial cell-to-cell communication mechanism and is based on gene regulatory networks, which control and regulate the production of signaling molecules in the environment. In the past years, mathematical modeling of quorum sensing has provided an understanding of key components of such networks, including several feedback loops involved. This paper presents a simple system of delay differential equations (DDEs) for quorum sensing of Pseudomonas putida with one positive feedback plus one (delayed) negative feedback mechanism. Results are shown concerning fundamental properties of solutions, such as existence, uniqueness, and non-negativity; the last feature is crucial for mathematical models in biology and is often violated when working with DDEs. The qualitative behavior of solutions is investigated, especially the stationary states and their stability. It is shown that for a certain choice of parameter values, the system presents stability switches with respect to the delay. On the other hand, when the delay is set to zero, a Hopf bifurcation might occur with respect to one of the negative feedback parameters. Model parameters are fitted to experimental data, indicating that the delay system is sufficient to explain and predict the biological observations.

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Systems analysis of a quorum sensing network: Design constraints imposed by the functional requirements, network topology and kinetic constants

Cited by 84 publications

References 35 publications

The rcsA Promoter of Pantoea stewartii subsp. stewartii Features a Low-Level Constitutive Promoter and an EsaR Quorum-Sensing-Regulated Promoter

The rcsA Promoter of Pantoea stewartii subsp. stewartii Features a Low-Level Constitutive Promoter and an EsaR Quorum-Sensing-Regulated Promoter

Network Robustness Due to Multiple Positive Feedback Loops: A Systematic Study of a Th Cell Differentiation Model

Mathematical Modeling of Bacteria Communication in Continuous Cultures

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