Chemotaxis in Escherichia coli: A Molecular Model for Robust Precise Adaptation

Department of Physics, Princeton University, Princeton, New Jersey, United States of America.
PLoS Computational Biology (Impact Factor: 4.62). 02/2008; 4(1):e1. DOI: 10.1371/journal.pcbi.0040001
Source: PubMed


The chemotaxis system in the bacterium Escherichia coli is remarkably sensitive to small relative changes in the concentrations of multiple chemical signals over a broad range of ambient concentrations. Interactions among receptors are crucial to this sensitivity as is precise adaptation, the return of chemoreceptor activity to prestimulus levels in a constant chemoeffector environment. Precise adaptation relies on methylation and demethylation of chemoreceptors by the enzymes CheR and CheB, respectively. Experiments indicate that when transiently bound to one receptor, these enzymes act on small assistance neighborhoods (AN) of five to seven receptor homodimers. In this paper, we model a strongly coupled complex of receptors including dynamic CheR and CheB acting on ANs. The model yields sensitive response and precise adaptation over several orders of magnitude of attractant concentrations and accounts for different responses to aspartate and serine. Within the model, we explore how the precision of adaptation is limited by small AN size as well as by CheR and CheB kinetics (including dwell times, saturation, and kinetic differences among modification sites) and how these kinetics contribute to noise in complex activity. The robustness of our dynamic model for precise adaptation is demonstrated by randomly varying biochemical parameters.

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Available from: Robert Endres, Mar 23, 2014
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    • "It describes an organism's response to an external perturbation by returning state variables to their original values before perturbation. For example, perfect adaptation has been reported in bacterial (e.g., E. coli) chemotaxis (Berg and Tedesco, 1975; Alon et al., 1999; Yi et al., 2000; Hansen et al., 2008), osmotic-stress adaptations (Muzzey et al., 2009), and MAP-kinase regulation (Hao et al., 2007; Mettetal et al., 2008). Such perfect adaption behaviors are thought to be introduced through a time integral on the " controlled variable " in the network , which corresponds to a specific control system structure, i.e., an integral feedback control (Csete and Doyle, 2002). "
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    ABSTRACT: Living organisms persist by virtue of complex interactions among many components organized into dynamic, environment-responsive networks that span multiple scales and dimensions. Biological networks constitute a type of Information and Communication Technology (ICT): they receive information from the outside and inside of cells, integrate and interpret this information, and then activate a response. Biological networks enable molecules within cells, and even cells themselves, to communicate with each other and their environment. We have become accustomed to associating brain activity – particularly activity of the human brain – with a phenomenon we call “intelligence”. Yet, four billion years of evolution could have selected networks with topologies and dynamics that confer traits analogous to this intelligence, even though they were outside the intercellular networks of the brain. Here, we explore how macromolecular networks in microbes confer intelligent characteristics, such as memory, anticipation, adaptation and reflection and we review current understanding of how network organization reflects the type of intelligence required for the environments in which they were selected. We propose that, if we were to leave terms such as “human” and “brain” out of the defining features of “intelligence”, all forms of life – from microbes to humans – exhibit some or all characteristics consistent with “intelligence”. We then review advances in genome-wide data production and analysis, especially in microbes, that provide a lens into microbial intelligence and propose how the insights derived from quantitatively characterizing biomolecular networks may enable synthetic biologists to create intelligent molecular networks for biotechnology, possibly generating new forms of intelligence, first in silico and then in vivo.
    Full-text · Article · Jul 2014 · Frontiers in Microbiology
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    • "Transmembrane methyl-accepting chemotaxis proteins (MCPs) of motile bacteria are responsible for sensing chemoattractants in the environment (Fernando et al., 2007; Zhulin, 2001). The combination of MCPs with chemoattractants causes the activation of intracellular CheA histidine kinase to trigger the MCPs-dependent signalling pathway, in which the CheA activates the CheY response regulator that controls the flagellar rotation direction (Hansen et al., 2008; Stecher et al., 2004). Subsequently, the bacteria depend on flagellar directional movement to reach suitable sites in tissues for colonization (Moisi et al., 2009; Williams et al., 2007). "
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    ABSTRACT: Methyl-accepting chemotaxis proteins (MCPs), also termed transducer-like proteins (Tlps), serve as sensors in bacterial chemotactic signaling, which detect attractants and promote bacterial movement towards suitable sites for colonization. Campylobacter jejuni is a leading cause of human enteritis, but the mechanisms responsible for bacterial chemotaxis and early colonization in jejunum of hosts are poorly understood. In the present study, we identify several types of bile and sodium deoxycholate (SDC) to act as chemotactic attractants of C. jejuni strain NCTC11168-O in vitro, in which SDC was the most efficient chemoattractant. In mice with bile duct ligation, the wild-type strain displayed a markedly attenuated ability for colonization. Blockage of Tlp3 or Tlp4 protein with antibody or disruption of the tlp3 or tlp4 gene (Δtlp3 or Δtlp4) caused the significant inhibition of SDC-induced chemotaxis and attenuation for colonization on jejunal mucosa in mice of the bacterium. Disruption of both the two genes (Δtlp3-Δtlp4) resulted in the absence of bacterial chemotaxis and colonization, while the tlp-gene-complemented mutants (CΔtlp3 and CΔtlp4) reacquired these abilities. The results indicate that SDC is an effective chemoattractant for C. jejuni, and Tlp3 and Tlp4 are the SDC-specific sensor proteins responsible for the bacterial chemoattraction.
    Full-text · Article · Jan 2014 · Journal of Medical Microbiology
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    • "A phosphatase, CheZ, dephosphorylates CheY-P. The chemotaxis pathway is well known for its high gain8,10–11, wide dynamic range11–12, and robust adaptation5,13, mediated by receptor methylation and demethylation (by CheR and CheB). "
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    ABSTRACT: In the bacterial chemotaxis network, receptor clusters process input, and flagellar motors generate output. Receptor and motor complexes are coupled by the diffusible protein CheY-P. Receptor output (the steady-state concentration of CheY-P) varies from cell to cell. However, the motor is ultrasensitive, with a narrow operating range of CheY-P concentrations. How the match between receptor output and motor input might be optimized is unclear. Here we show that the motor can shift its operating range by changing its composition. The number of FliM subunits in the C-ring increases in response to a decrement in the concentration of CheY-P, increasing motor sensitivity. This shift in sensitivity explains the slow partial adaptation observed in mutants that lack the receptor methyltransferase and methylesterase and why motors show signal-dependent FliM turnover. Adaptive remodelling is likely to be a common feature in the operation of many molecular machines.
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