SUMMARY: Two-component signal-transducing systems are ubiquitously distributed communication interfaces in bacteria. They consist of a histidine kinase that senses a specific environmental stimulus and a cognate response regulator that mediates the cellular response, mostly through differential expression of target genes. Histidine kinases are typically transmembrane proteins harboring at least two domains: an input (or sensor) domain and a cytoplasmic transmitter (or kinase) domain. They can be identified and classified by virtue of their conserved cytoplasmic kinase domains. In contrast, the sensor domains are highly variable, reflecting the plethora of different signals and modes of sensing. In order to gain insight into the mechanisms of stimulus perception by bacterial histidine kinases, we here survey sensor domain architecture and topology within the bacterial membrane, functional aspects related to this topology, and sequence and phylogenetic conservation. Based on these criteria, three groups of histidine kinases can be differentiated. (i) Periplasmic-sensing histidine kinases detect their stimuli (often small solutes) through an extracellular input domain. (ii) Histidine kinases with sensing mechanisms linked to the transmembrane regions detect stimuli (usually membrane-associated stimuli, such as ionic strength, osmolarity, turgor, or functional state of the cell envelope) via their membrane-spanning segments and sometimes via additional short extracellular loops. (iii) Cytoplasmic-sensing histidine kinases (either membrane anchored or soluble) detect cellular or diffusible signals reporting the metabolic or developmental state of the cell. This review provides an overview of mechanisms of stimulus perception for members of all three groups of bacterial signal-transducing histidine kinases.

Escherichia coli contains a versatile respiratory chain that oxidizes 10 different electron donor substrates and transfers the electrons to terminal reductases or oxidases for the reduction of six different electron acceptors. Salmonella is able to use two more electron acceptors. The variation is further increased by the presence of isoenzymes for some substrates. A large number of respiratory pathways can be established by combining different electron donors and acceptors. The respiratory dehydrogenases use quinones as the electron acceptors that are oxidized by the terminal reductase and oxidases. The enzymes vary largely with respect to their composition, architecture, membrane topology, and the mode of energy conservation. Most of the energy-conserving dehydrogenases (FdnGHI, HyaABC, HybCOAB, and others) and the terminal reductases (CydAB, NarGHI, and others) form a proton potential (Δ p ) by a redox-loop mechanism. Two enzymes (NuoA-N and CyoABCD) couple the redox energy to proton translocation by proton pumping. A large number of dehydrogenases and terminal reductases do not conserve the redox energy in a proton potential. For most of the respiratory enzymes, the mechanism of proton potential generation is known or can be predicted. The H ⁺ /2e ⁻ ratios for most respiratory chains are in the range from 2 to 6 H ⁺ /2e ⁻ . The energetics of the individual redox reactions and the respiratory chains is described and related to the H ⁺ /2e ⁻ ratios.

Thiosulfate respiration in Salmonella enterica serovar Typhimurium is catalyzed by the membrane-bound enzyme thiosulfate reductase. Experiments with quinone biosynthesis mutants show that menaquinol is the sole electron donor to thiosulfate reductase. However, the reduction of thiosulfate by menaquinol is highly endergonic under standard conditions (Δ E °′ = −328 mV). Thiosulfate reductase activity was found to depend on the proton motive force (PMF) across the cytoplasmic membrane. A structural model for thiosulfate reductase suggests that the PMF drives endergonic electron flow within the enzyme by a reverse loop mechanism. Thiosulfate reductase was able to catalyze the combined oxidation of sulfide and sulfite to thiosulfate in a reverse of the physiological reaction. In contrast to the forward reaction the exergonic thiosulfate-forming reaction was PMF independent. Electron transfer from formate to thiosulfate in whole cells occurs predominantly by intraspecies hydrogen transfer.

C ₄ -dicarboxylates and the C ₄ -dicarboxylic amino acid l -aspartate support aerobic and anaerobic growth of Escherichia coli and related bacteria. In aerobic growth, succinate, fumarate, D - and L -malate, L -aspartate, and L -tartrate are metabolized by the citric acid cycle and associated reactions. Because of the interruption of the citric acid cycle under anaerobic conditions, anaerobic metabolism of C ₄ -dicarboxylates depends on fumarate reduction to succinate (fumarate respiration). In some related bacteria (e.g., Klebsiella ), utilization of C ₄ -dicarboxylates, such as tartrate, is independent of fumarate respiration and uses a Na ⁺ -dependent membrane-bound oxaloacetate decarboxylase. Uptake of the C ₄ -dicarboxylates into the bacteria (and anaerobic export of succinate) is achieved under aerobic and anaerobic conditions by different sets of secondary transporters. Expression of the genes for C ₄ -dicarboxylate metabolism is induced in the presence of external C ₄ -dicarboxylates by the membrane-bound DcuS-DcuR two-component system. Noncommon C ₄ -dicarboxylates like l -tartrate or D -malate are perceived by cytoplasmic one-component sensors/transcriptional regulators. This article describes the pathways of aerobic and anaerobic C ₄ -dicarboxylate metabolism and their regulation. The citric acid cycle, fumarate respiration, and fumarate reductase are covered in other articles and discussed here only in the context of C ₄ -dicarboxylate metabolism. Recent aspects of C ₄ -dicarboxylate metabolism like transport, sensing, and regulation will be treated in more detail. This article is an updated version of an article published in 2004 in EcoSal Plus . The update includes new literature, but, in particular, the sections on the metabolism of noncommon C ₄ -dicarboxylates and their regulation, on the DcuS-DcuR regulatory system, and on succinate production by engineered E. coli are largely revised or new.