A number of genes and

enzymes responsible for synthesis, uptake and efflux of compatible solutes have been identified in diverse bacteria [1, 6–10]. However, the mechanisms by which bacteria sense osmotic shifts (osmosensing) PKC412 mouse and the signal transduction pathways leading to these genes (osmosignaling) have focused on membrane-based osmosensors from moderately halotolerant, but not halophilic, bacteria. These include osmosensory transporters, histidine AZD8931 kinases of two-component transcriptional regulatory systems [9], and mechanosensitive channels of the MscL, MscS and MscK type [6]. Whereas the first and the third group can detect osmotic pressure Nutlin-3a supplier changes and respond by mediating compatible solute uptake or efflux, respectively, without the assistance of other proteins, membrane-bound histidine kinases detect changes in osmotic pressure and other signals and then respond by directing cognate response regulators to modulate transcription of osmoregulated genes. The best studied osmosensory transporters mediate uptake of potassium, i.e. Trk from Escherichia

coli, and betaine, such as ProP from E. coli, OpuA from Lactococcus lactis and BetP from Corynebacterium glutamicum [9, 11]. On the other hand, the best characterized two-component transcriptional regulatory systems involved in bacterial osmoadaptation are KdpDE and EnvZ/OmpR from E. coli, and MtrAB

from C. glutamicum [11–13]. Both sensory DAPT histidine protein kinases and response regulators of two-component signal transduction systems are multi-domain proteins. Histidine protein kinases typically consist of a variable N-terminal sensory or “”input”" domain, which detects environmental stimuli and activates a conserved C-terminal cytoplasmic transmitter domain, comprising an ATP-binding kinase domain and a histidine-containing dimerization domain. On the other hand, most response regulators contain a conserved N-terminal receiver (REC) domain and a variable C-terminal effector or “”output”" domain. The first one catalyzes the transfer of the phosphoryl group from the cognate histidine protein kinase to one of its own aspartic residues. As a result, the receiver domain undergoes a conformational change capable of promoting activity of the effector domain [14, 16]. Two general approaches have been used for classifying bacterial two-component systems. The first one is based on the diversity of input (i.e. cellular location, membrane topology, arrangement of sensory domains) or output (i.e., DNA-binding, RNA-binding, protein-binding, enzymatic, etc) domain architecture and domain combinations [14, 15, 17]. The second one is based on the phylogeny of transmitter and receiver domains [18].