The three adaptation systems of Bacillus subtilis chemotaxis

Abstract

Adaptation has a crucial role in the gradient-sensing mechanism that underlies bacterial chemotaxis. The Escherichia coli chemotaxis pathway uses a single adaptation system involving reversible receptor methylation. In Bacillus subtilis, the chemotaxis pathway seems to use three adaptation systems. One involves reversible receptor methylation, although quite differently than in E. coli. The other two involve CheC, CheD and CheV, which are chemotaxis proteins not found in E. coli. Remarkably, no one system is absolutely required for adaptation or is independently capable of generating adaptation. In this review, we discuss these three novel adaptation systems in B. subtilis and propose a model for their integration.

Figure 1

The adaptation process. The addition of attractant (+Att) causes a transient decrease in the concentration of CheYp in Escherichia coli, which leads to an increased likelihood of a smooth run. However, the change in CheYp concentrations is transitory because the pathway eventually adapts the concentration of CheYp to the addition of the attractant. In other words, the concentration of CheYp returns to prestimulus levels despite the presence of attractant. The removal of attractant (−Att), by contrast, increases the concentration of CheYp, which leads to a decreased likelihood of a smooth run or, alternatively, an increased likelihood of a reorientating tumble. As with addition, the pathway eventually adapts the concentration of the CheYp to the loss of attractant. The reciprocal process occurs in Bacillus subtilis: the addition of attractant causes an increase in CheYp concentration, and the removal of attractant causes a decrease in CheYp concentration. In B. subtilis, the frequency of runs is proportional to the concentration of CheYp, whereas, in E. coli, the frequency of runs is inversely proportional to the concentration of CheYp.

Figure 2

Model of the McpB structure in Bacillus subtilis. Based on homology to the Tm1143 chemoreceptor, the methylation sites (highlighted) form a tight cluster. Note that residue 371 is on a separate monomer of the chemoreceptor homodimer, opposite that of residues 630 and 637.

Figure 3

CheD and CheC interaction in Bacillus subtilis. Based on the Thermotoga maritima structure, Asp149 (blue) lies on the face of CheC that binds to CheD. The active site glutamate (green) and asparagine (red) residues are on the opposite side of the molecule, presumably where CheC interacts with CheYp.

Figure 4

Model for the CheC–CheD–CheYp adaptation system in Bacillus subtilis. (a) Prior to simulation with attractant, CheD is bound to receptors. (b) When attractant binds to the receptors, the CheA kinase is activated and more CheYp is formed. (c) Higher levels of CheYp lead to more CheC–CheYp complexes, which then attracts CheD away from the receptors. (d) Receptors unbound with CheD only weakly activate the CheA kinase, causing less CheYp to be formed (adaptation). In addition, the greater binding of CheD to CheC caused by the presence of CheYp also enhances CheYp dephosphorylation and thus ‘sharpens’ the response. Note that this mechanism is incapable of full adaptation because the strength of the negative feedback is proportional to CheA kinase activity. It is likely that only some of the CheD leaves the receptors, although the extent of association between CheD and the receptors remains unknown. Abbreviations: A, CheA; C, CheC; D, CheD; V, CheV; W, CheW; Y, CheY; Yp, CheYp.

Figure 5

Model for CheV adaptation system in Bacillus subtilis. Attractant binding activates the CheA kinase, leading to increased phosphorylation of CheY and CheV. Phosphorylated CheV (Vp) is then thought to inhibit kinase activity by disrupting the coupling between the receptors and CheA. The dashed box is used to emphasize that CheV is probably stably coupled to the receptors CheA and CheW. Abbreviations: A, CheA; V, CheV; W, CheW; Y, CheY; Yp, CheYp.