Chemotactic Response and Adaptation Dynamics in Escherichia coli

Adaptation of the chemotaxis sensory pathway of the bacterium Escherichia coli is integral for detecting chemicals over a wide range of background concentrations, ultimately allowing cells to swim towards sources of attractant and away from repellents. Its biochemical mechanism based on methylation and demethylation of chemoreceptors has long been known. Despite the importance of adaptation for cell memory and behavior, the dynamics of adaptation are difficult to reconcile with current models of precise adaptation. Here, we follow time courses of signaling in response to concentration step changes of attractant using in vivo fluorescence resonance energy transfer measurements. Specifically, we use a condensed representation of adaptation time courses for efficient evaluation of different adaptation models. To quantitatively explain the data, we finally develop a dynamic model for signaling and adaptation based on the attractant flow in the experiment, signaling by cooperative receptor complexes, and multiple layers of feedback regulation for adaptation. We experimentally confirm the predicted effects of changing the enzyme-expression level and bypassing the negative feedback for demethylation. Our data analysis suggests significant imprecision in adaptation for large additions. Furthermore, our model predicts highly regulated, ultrafast adaptation in response to removal of attractant, which may be useful for fast reorientation of the cell and noise reduction in adaptation.Author Summary: Bacterial chemotaxis is a paradigm for sensory systems, and thus has attracted immense interest from biologists and modelers alike. Using this pathway, cells can sense chemical molecules in their environment, and bias their movement towards nutrients and away from toxins. To avoid over- or understimulation of the signaling pathway, receptors adapt to current external conditions by covalent receptor modification, ultimately allowing cells to chemotax over a wide range of background concentrations. While the robustness and precision in adaptation was previously explained, we quantify the dynamics of adaptation, important for cell memory and behavior, as well as noise filtering in the pathway. Specifically, we study the intracellular signaling response and subsequent adaptation to concentration step changes in attractant chemicals. We combine measurements of signaling in living cells with a dynamic model for strongly coupled receptors, even including the effects of concentration flow in the experiment. Using a novel way of summarizing time-dependent data, we derive a new adaptation model, predicting additional layers of feedback regulation. As a consequence, adaptation to sudden exposure of unfavorable conditions is very fast, which may be useful for a quick reorientation and escape of the cell.