Co-expression of signaling proteins improves robustness of the bacterial chemotaxis pathway

Biological systems are exposed to various perturbations that affect performance of the cellular networks, with stochastic variation in protein levels, or gene expression noise, being one of the major sources of intracellular perturbations. We recently used Escherichia coli chemotaxis as a model to analyze robustness against such noise and demonstrated theoretically and experimentally that a steady-state output of the pathway is robust against concerted variation in the levels, of all chemotaxis proteins. However, our model predicted that the pathway topology does not confer much robustness against an uncorrelated variation in the protein levels. To test whether additional robustness features might be missing from our model, we compare here its predictions with an experimentally determined chemotactic performance under varying levels of individual proteins. Our data show that the pathway is indeed even more robust than predicted to two types of perturbations-the variation in the levels of the adaptation enzymes and a correlated expression of CheY and CheZ. Although the design features that are responsible for this higher robustness still remain to be understood, our results stress the importance of a robust design of both native and synthetic signaling networks. (c) 2007 Elsevier B.V. All rights reserved

Design principles of a bacterial signalling network

Cellular biochemical networks have to function in a noisy environment using imperfect components. In particular, networks involved in gene regulation or signal transduction allow only for small output tolerances, and the underlying network structures can be expected to have undergone evolution for inherent robustness against perturbations(1). Here we combine theoretical and experimental analyses to investigate an optimal design for the signalling network of bacterial chemotaxis, one of the most thoroughly studied signalling networks in biology. We experimentally determine the extent of intercellular variations in the expression levels of chemotaxis proteins and use computer simulations to quantify the robustness of several hypothetical chemotaxis pathway topologies to such gene expression noise. We demonstrate that among these topologies the experimentally established chemotaxis network of Escherichia coli has the smallest sufficiently robust network structure, allowing accurate chemotactic response for almost all individuals within a population. Our results suggest that this pathway has evolved to show an optimal chemotactic performance while minimizing the cost of resources associated with high levels of protein expression. Moreover, the underlying topological design principles compensating for intercellular variations seem to be highly conserved among bacterial chemosensory systems(2)