Feedback Control Architecture and the Bacterial Chemotaxis Network

Abstract

Bacteria move towards favourable and away from toxic environments by changing their swimming pattern. This response is regulated by the chemotaxis signalling pathway, which has an important feature: it uses feedback to ‘reset’ (adapt) the bacterial sensing ability, which allows the bacteria to sense a range of background environmental changes. The role of this feedback has been studied extensively in the simple chemotaxis pathway of Escherichia coli. However it has been recently found that the majority of bacteria have multiple chemotaxis homologues of the E. coli proteins, resulting in more complex pathways. In this paper we investigate the configuration and role of feedback in Rhodobacter sphaeroides, a bacterium containing multiple homologues of the chemotaxis proteins found in E. coli. Multiple proteins could produce different possible feedback configurations, each having different chemotactic performance qualities and levels of robustness to variations and uncertainties in biological parameters and to intracellular noise. We develop four models corresponding to different feedback configurations. Using a series of carefully designed experiments we discriminate between these models and invalidate three of them. When these models are examined in terms of robustness to noise and parametric uncertainties, we find that the non-invalidated model is superior to the others. Moreover, it has a ‘cascade control’ feedback architecture which is used extensively in engineering to improve system performance, including robustness. Given that the majority of bacteria are known to have multiple chemotaxis pathways, in this paper we show that some feedback architectures allow them to have better performance than others. In particular, cascade control may be an important feature in achieving robust functionality in more complex signalling pathways and in improving their performance.

Feedback control architecture of the R. sphaeroides chemotaxis network

“…We then review the main result of [6]. In light of the discussion of linear cascade control systems, we demonstrate that the (nonlinear) model suggested by [6] is structurally similar to the cascade control architecture.…”

“…We then review the main result of [6]. In light of the discussion of linear cascade control systems, we demonstrate that the (nonlinear) model suggested by [6] is structurally similar to the cascade control architecture. Furthermore, the model shares with this architecture several properties, including the sensitivity re-distribution and disturbance rejection features for which this control scheme is employed in engineering applications, suggesting that this structure may be the result of evolutionary advantages arising from increased robustness.…”

“…In [6], an integrated model of this chemotaxis pathway was presented. It was assumed that as a dynamical system, this pathway had several parallels to that of E. coli, including the integral feedback controller responsible for adaptation.…”

“…The additional degrees of freedom thus create the potential for improved feedback regulation. The additional receptor cluster not found in E. coli may be the source of disturbances, and one of the feedback architectures in [6] was shown to be superior in reducing the system's sensitivity to this and other sources of uncertainty such as protein copy number variations.…”

Tools used to study how protein complexes are assembled in signaling cascades

“…For example, several hundred protein-protein interactions in yeast have also been identified for the corresponding protein orthologs in worm, 5,6 and the signaling pathways that control chemotaxis in bacteria have very clear similiarities to the processes that control cell migration in immune cells in higher species. [7][8][9][10] As well as the signaling pathways, the rules dictating protein-protein interactions and complex formation are highly conserved. The past 15 years has seen the development of a large number of methods which have propelled our understanding of signaling cascades by helping us identify and characterize protein-protein interactions and signaling networks.…”