Responding to chemical gradients: bacterial chemotaxis

Abstract

Chemotaxis allows bacteria to follow gradients of nutrients and other environmental stimuli. The bacterium Escherichia coli performs chemotaxis via a run-and-tumble strategy in which sensitive temporal comparisons lead to a biased random walk, with longer runs in the preferred gradient direction. The chemotaxis network of E. coli has developed over the years into one of the most thoroughly studied model systems for signal transduction and behavior, yielding general insights into such properties of cellular networks as signal amplification, signal integration, and robustness. Despite its relative simplicity, the operation of the E. coli chemotaxis network is highly refined and evolutionarily optimized at many levels. For example, recent studies revealed that the network adjusts its signaling properties dependent on the extracellular environment, apparently to optimize chemotaxis under particular conditions. The network can even utilize potentially detrimental stochastic fluctuations in protein levels and reaction rates to maximize the chemotactic performance of the population.

Box Figure

Figure 1. Chemotaxis strategy of Escherichia coli

(A) Swimming of E. coli in the absence of a gradient. Movement of E. coli cells in a uniform environment consists of smooth runs that last up to several seconds and are interrupted by short (~0.1 sec) tumbles. Runs result from the counterclockwise (CCW) rotation of flagella, which results in formation of a propelling flagellar bundle behind the cell. Tumbles are caused by the clockwise (CW) rotation of one or several flagella, which destabilizes the bundle. Tumbles randomly reorient the cell body before the next run, with the angle of reorientation (indicated by red arrow) being dependent on the number of CW-rotating flagella [43]. The resulting random walk ensures effective foraging in the environment, and may be further enhanced by occasional long runs (green) resulting from stochastic fluctuation in the pathway activity. (B) Chemotaxis in gradients. The chemotaxis strategy of E. coli and other bacteria is based on a biased random walk, whereby cells make temporal comparisons of chemoeffector concentrations during a run and suppress the onset of the next tumble if the level of positive stimulation increases. As a consequence, runs in the positive direction (i.e., up the chemoattractant gradient) are prolonged. Moreover, since on average fewer flagella participate in tumbles when cells are moving up the gradient, the degree of cell body reorientation during such tumbles is smaller. The magnitude of response to the gradient depends on the change in attractant concentration (Δc) experienced by the swimming cell during a run before the cell’s memory is reset by the adaptation system, with the typical run time ~1 s and the corresponding measurement distance ~20 μm.

Figure 2. Spatial organization of the chemosensory machinery

(A) Cellular distribution of chemotaxis and motor proteins. The receptor-kinase sensory complexes and associated chemotaxis proteins are organized into large macromolecular clusters that are visible at the cell poles and along the cell body in fluorescence images. Here receptor clusters are labeled by CheR-CFP (cyan) that directly binds to receptors. Also shown is the cellular distribution of flagellar motors labeled by FliM-YFP (red). (B) Receptor arrangement in clusters. Cryo-electron microscopy image showing a honeycomb lattice of trimers of receptor dimers (courtesy of Ariane Briegel and Grant J Jensen, based on [69] and reproduced from [5]). Individual hexagons of trimers within the lattice are highlighted in red. (C,D) Regulation of allosteric interactions between receptors in clusters. Receptors in clusters are believed to function as allosteric signaling teams of ~2-6 mixed trimers of dimers, with all receptors in a team switching cooperatively between active (i.e. kinase-activating) and inactive (i.e. kinase-inactivating) states, thereby amplifying and integrating chemotactic signals. (C) Regulation of cooperativity among receptors in clusters. High expression levels of receptors and other chemotaxis proteins in nutrient-poor medium results in higher receptor density and higher cooperativity (i.e. signaling team size) (right panel; red indicates one signaling team). (D) Regulation of ligand preference within signaling teams. Receptor dimers of different specificities (green: serine receptor Tsr, magenta: aspartate receptor Tar) are mixed within teams (only one team is shown). Because each team’s response is determined by the total number of bound ligands, higher expression of Tar (as observed at high cell density) changes the ligand preference of the team from serine to aspartate.