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Register a new userEffect of receptor clustering on chemotactic performance of Escherichia coli: sensing versus adaptation
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We show how the competition between sensing and adaptation can result in a performance peak in E.coli chemotaxis using extensive numerical simulations in a detailed theoretical model. Receptor clustering amplifies the input signal coming from ligand binding which enhances chemotactic efficiency. But large clusters also induce large fluctuations in total activity since the number of clusters go down. The activity and hence the run-tumble motility now gets controlled by methylation levels which are part of adaptation module, rather than ligand binding. This reduces chemotactic efficiency.
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In response to a concentration gradient of nutrient, E. coli bacterium modulates the rotational bias of flagellar motors which control its run-and-tumble motion, to migrate towards regions of high nutrient concentration. Presence of stochastic noise in the biochemical pathway of the cell has important consequence on the switching mechanism of motor bias, which in turn affects the runs and tumbles of the cell. We model the intra-cellular reaction network in terms of coupled time-evolution of three stochastic variables, kinase activity, methylation level and CheY-P protein level, and study the effect of methylation noise on the chemotactic performance of the cell. In presence of a spatially varying nutrient concentration profile, a good chemotactic performance allows the cell to climb up the concentration gradient fast and localize in the nutrient-rich regions in the long time limit. Our simulations show that the best performance is obtained at an optimal noise strength. While it is expected that chemotaxis will be weaker for very large noise, it is counter-intuitive that the performance worsens even when noise level falls below a certain value. We explain this striking result by detailed analysis of CheY-P protein level statistics for different noise strengths. We show that when the CheY-P level falls below a certain (noise-dependent) threshold, the cell tends to move down the concentration gradient of the nutrient, which has a detrimental effect on its chemotactic response. This threshold value decreases as noise is increased, and this effect is responsible for noise-induced enhancement of chemotactic performance. In a harsh chemical environment, when the nutrient degrades with time, the amount of nutrient intercepted by the cell trajectory, is an effective performance criterion. In this case also, we find an optimum noise strength, depending on the nutrient lifetime.
We have developed a mathematical model of regulation of expression of the Escherichia coli lac operon, and have investigated bistability in its steady-state induction behavior in the absence of external glucose. Numerical analysis of equations describing regulation by artificial inducers revealed two natural bistability parameters that can be used to control the range of inducer concentrations over which the model exhibits bistability. By tuning these bistability parameters, we found a family of biophysically reasonable systems that are consistent with an experimentally determined bistable region for induction by thio-methylgalactoside (Ozbudak et al. Nature 427:737, 2004). The model predicts that bistability can be abolished when passive transport or permease export becomes sufficiently large; the former case is especially relevant to induction by isopropyl-beta, D-thiogalactopyranoside. To model regulation by lactose, we developed similar equations in which allolactose, a metabolic intermediate in lactose metabolism and a natural inducer of lac, is the inducer. For biophysically reasonable parameter values, these equations yield no bistability in response to induction by lactose; however, systems with an unphysically small permease-dependent export effect can exhibit small amounts of bistability for limited ranges of parameter values. These results cast doubt on the relevance of bistability in the lac operon within the natural context of E. coli, and help shed light on the controversy among existing theoretical studies that address this issue. The results also suggest an experimental approach to address the relevance of bistability in the lac operon within the natural context of E. coli.
The polarisation of cells and tissues is fundamental for tissue morphogenesis during biological development and regeneration. A deeper understanding of biological polarity pattern formation can be gained from the consideration of pattern reorganisation in response to an opposing instructive cue, which we here consider by example of experimentally inducible body axis
Complex biological systems are very robust to genetic and environmental changes at all levels of organization. Many biological functions of Escherichia coli metabolism can be sustained against single-gene or even multiple-gene mutations by using redundant or alternative pathways. Thus, only a limited number of genes have been identified to be lethal to the cell. In this regard, the reaction-centric gene deletion study has a limitation in understanding the metabolic robustness. Here, we report the use of flux-sum, which is the summation of all incoming or outgoing fluxes around a particular metabolite under pseudo-steady state conditions, as a good conserved property for elucidating such robustness of E. coli from the metabolite point of view. The functional behavior, as well as the structural and evolutionary properties of metabolites essential to the cell survival, was investigated by means of a constraints-based flux analysis under perturbed conditions. The essential metabolites are capable of maintaining a steady flux-sum even against severe perturbation by actively redistributing the relevant fluxes. Disrupting the flux-sum maintenance was found to suppress cell growth. This approach of analyzing metabolite essentiality provides insight into cellular robustness and concomitant fragility, which can be used for several applications, including the development of new drugs for treating pathogens.
Photonic crystal-based biosensors hold great promise as valid and low-cost devices for real-time monitoring of a variety of biotargets. Given the high processability and easiness of read-out even for unskilled operators, these systems can be highly appealing for the detection of bacterial contaminants in food and water. Here, we propose a novel hybrid plasmonic/photonic device that is responsive to Escherichia coli, which is one of the most hazardous pathogenic bacterium. Our system consists of a thin layer of silver, a metal that exhibits both a plasmonic behavior and a well-known biocidal activity, on top of a solution processed 1D photonic crystal. We attribute the bio-responsivity to the modification of the dielectric properties of the silver film upon bacterial contamination, an effect that likely stems from the formation of polarization charges at the Ag/bacterium interface within a sort of bio-doping mechanism. Interestingly, this triggers a blue-shift in the photonic response. This work demonstrates that our hybrid plasmonic/photonic device can be a low-cost and portable platform for the detection of common contaminants in food and water.
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