Bacteria sense and respond to a wide range of physical and chemical signals. Central to sensing and responding to these signals are two-component systems, which have a sensor histidine kinase (SK) and a response regulator (RR) as basic components. Here we review the different molecular mechanisms by which these signals are integrated and modulate the phosphorylation state of SKs. Apart from the basic mechanism, which consists of signal recognition by the SK that leads to an alteration of its autokinase activity and subsequently a change in the RR phosphorylation state, a variety of alternative modes have evolved. The biochemical data available on SKs, particularly their molecular interactions with signals, nucleotides, and their cognate RRs, are also reviewed.

Summary: Central to the different forms of taxis are methyl‐accepting chemotaxis proteins (MCPs). The increasing number of genome sequences reveals that MCPs differ enormously in sequence, topology and genomic abundance. This work is a one‐by‐one bioinformatic analysis of the almost‐totality of MCP genes available and a classification of motile bacteria according to their lifestyle. On average, motile archaea have 6.7 MCP genes per genome whereas motile bacteria have more than twice as much. We show that the number of MCPs per genome depends on bacterial lifestyle and metabolic diversity, but weakly on genome size. Signal perception at an MCP occurs at the N‐terminal ligand binding region (LBR). Here we show that around 88% of MCPs possess an LBR that remains un‐annotated in SMART. MCPs can be classified into two clusters according to the size of the LBR. Cluster I receptors have an LBR between 120 and 210 amino acids whereas cluster II receptors have larger LBRs of 220–299 amino acids. There is evidence that suggests that some cluster II LBRs are composed of two cluster I LBRs. Further evidence indicates that other cluster II LBRs might harbour novel sensor domains. Cluster II receptors are dominant in archaea whereas cluster I receptors are prevalent in bacteria. MCPs can be classified into six different receptor topologies and this work contains a first estimation of the relative abundance of different receptor topologies in bacteria and archaea. Topologies involving extracytoplasmic sensing are prevalent in bacteria whereas topologies with cytosolic signal recognition are abundant in archaea.

Summary: Bacterial taxis is one of the most investigated signal transduction mechanisms. Studies of taxis have primarily used Escherichia coli and Salmonella as model organism. However, more recent studies of other bacterial species revealed a significant diversity in the chemotaxis mechanisms which are reviewed here. Differences include the genomic abundance, size and topology of chemoreceptors, the mode of signal binding, the presence of additional cytoplasmic signal transduction proteins or the motor mechanism. This diversity of chemotactic mechanisms is partly due to the diverse nature of input signals. However, the physiological reasons for the majority of differences in the taxis systems are poorly understood and its elucidation represents a major research need.

We report the identification of McpS as the specific chemoreceptor for 6 tricarboxylic acid (TCA) cycle intermediates and butyrate in Pseudomonas putida. The analysis of the bacterial mutant deficient in mcpS and complementation assays demonstrate that McpS is the only chemoreceptor of TCA cycle intermediates in the strain under study. TCA cycle intermediates are abundantly present in root exudates, and taxis toward these compounds is proposed to facilitate the access to carbon sources. McpS has an unusually large ligand-binding domain (LBD) that is un-annotated in InterPro and is predicted to contain 6 helices. The ligand profile of McpS was determined by isothermal titration calorimetry of purified recombinant LBD (McpS-LBD). McpS recognizes TCA cycle intermediates but does not bind very close structural homologues and derivatives like maleate, aspartate, or tricarballylate. This implies that functional similarity of ligands, such as being part of the same pathway, and not structural similarity is the primary element, which has driven the evolution of receptor specificity. The magnitude of chemotactic responses toward these 7 chemoattractants, as determined by qualitative and quantitative chemotaxis assays, differed largely. Ligands that cause a strong chemotactic response (malate, succinate, and fumarate) were found by differential scanning calorimetry to increase significantly the midpoint of protein unfolding (T_m) and unfolding enthalpy (ΔH) of McpS-LBD. Equilibrium sedimentation studies show that malate, the chemoattractant that causes the strongest chemotactic response, stabilizes the dimeric state of McpS-LBD. In this respect clear parallels exist to the Tar receptor and other eukaryotic receptors, which are discussed.

Summary: Bacterial chemotaxis is an adaptive behaviour, which requires sophisticated information‐processing capabilities that cause motile bacteria to either move towards or flee from chemicals. Pseudomonas putida DOT‐T1E exhibits the capability to move towards different aromatic hydrocarbons present at a wide range of concentrations. The chemotactic response is mediated by the McpT chemoreceptor encoded by the pGRT1 megaplasmid. Two alleles of mcpT are borne on this plasmid and inactivation of either one led to loss of this chemotactic phenotype. Cloning of mcpT into a plasmid complemented not only the mcpT mutants but also its transfer to other Pseudomonas conferred chemotactic response to high concentrations of toluene and other chemicals. Therefore, the phenomenon of chemotaxis towards toxic compounds at high concentrations is gene‐dose dependent. In vitro experiments show that McpT is methylated by CheR and McpT net methylation was diminished in the presence of hydrocarbons, what influences chemotactic movement towards these chemicals.