from David E. Whitworth writing in Bacterial Regulatory Networks:

Two-component systems (TCSs) are signalling pathways found abundantly in prokaryotes, and they are the dominant mechanism for stimulus-responsive adaptation in such organisms. An ever-increasing number of physiological phenomena are known to be regulated by TCSs, including cell cycle progression, pathogenesis, motility, and biofilm formation. The basic TCS comprises a receptor protein (sensor kinase) which autophosphorylates in response to a stimulus. The phosphoryl group is then directly transferred to a response regulator protein (the second component) that has a phosphorylation-dependent effector function. While the most basic TCSs are relatively well understood, there are many 'atypical' systems, which exhibit additional mechanistic features (for instance, regulation of sub-cellular location, intrinsic and extrinsic phosphatase activities, and cross-communication between TCSs), adding complexity to their signalling properties. The relatively recent availability of complete prokaryotic genome sequences has also provided new opportunities to appreciate global features of TCS function. For example, analyses have provided insights into TCS evolution, which in turn have yielded computational methods for evaluating TCS protein partnerships. This chapter provides an overview of the common features of TCSs from a historical perspective, and then describes current understanding regarding the mechanisms of TCS function. Finally, outstanding questions regarding TCS function are discussed.

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from Efthimia Lioliou, Cédric Romilly, Thomas Geissmann, François Vandenesch and Pascale Romby writing in Bacterial Regulatory Networks:

Many pathogenic bacteria cause serious diseases in humans, animals, and plants. Due to the appearance of resistance to multiple antibiotics, it has become important to fully understand the regulatory networks that lead to the production of virulence factors that help the bacteria combat the host defense machinery, acquire nutrients, and survive and/or proliferate within the host. In recent years, complex interplays between transcriptional regulatory proteins, two-component systems, and regulatory RNAs have been described, establishing the gene expression patterns in pathogenic bacteria. In this review, several examples will illustrate the diversity of regulatory RNAs and how they are integrated into the regulatory circuits required for virulence gene expression, with special emphasis on the mechanisms of regulation at the molecular level.

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from Pierre Cornelis and Simon C. Andrews writing in Bacterial Regulatory Networks:

For the vast majority of bacteria, iron is an essential element that is not readily available due to the poor solubility of the oxidized Fe³⁺ form that prevails aerobically. Because of this, bacteria inhabiting aerobic niches often suffer deficiencies in iron supply. Pathogenic bacteria experience a particularly acute form of iron-restriction. This arises from the host's 'iron-withdrawal response' to infection, whereby iron availability is constrained by increasing lactoferrin (an iron-chelating, bacteriostatic, extracellular glycoprotein) levels and reducing the degree of iron saturation for the circulating iron-transport protein, transferrin. The importance of iron to bacteria stems from its multiple metabolic roles. Examples of its crucial metabolic involvement include redox-stress resistance (e.g. heme-bearing catalases) and DNA manufacture (di-Fe containing ribonucleotide reductases). Although indispensible, iron is an unfriendly, hazardous metal as the Fe²⁺-triggered Fenton reaction produces destructive reactive oxygen species (ROS) such as superoxide (O2^-), hydrogen peroxide (H₂O₂) as well as the highly reactive hydroxyl radical (^˚OH).

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from Zulma R. Suárez-Moreno, Juan F. González, Giulia Devescovi and Vittorio Venturi writing in Bacterial Regulatory Networks:

Bacteria regulate gene expression in a population dependent manner using a sophisticated mechanism based on the production and sensing of chemical signals, known as quorum sensing. Such synchronized response in bacterial populations constitutes a form of multicellularity and enables adaption and survival in challenging environments. Although current evidence shows that the predominant signaling molecules produced by Gram-negative bacteria are N-acyl derivatives of homoserine lactones (AHLs), bacteria use a wide variety of signals. In this chapter we provide an overview of quorum sensing in Gram-negative bacteria, and discuss current and future trends in this field of research.

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from Charles J. Dorman writing in Bacterial Regulatory Networks:

H-NS is an abundant DNA binding protein that has been found to influence the expression of hundreds of genes in those Gram-negative bacteria, chiefly Escherichia coli and Salmonella enterica, where its regulatory effects have been investigated. It also has the potential to organize the structure of the nucleoid. H-NS has a preference for binding to A+T-rich DNA and this preference underlies its targeting of genes that have been acquired by horizontal transfer. H-NS usually acts as a transcriptional silencer by binding to a nucleation site followed by lateral spreading with or without the creation of DNA-protein-DNA bridges; it may also act as an architectural component in the nucleoid. Bacteria use a multitude of mechanisms to displace H-NS or to attenuate its negative influence on gene expression. A paralogue of H-NS, called StpA, is an efficient RNA chaperone and controls a regulon of genes in S. enterica by influencing expression of the RpoS sigma factor. Orthologues of H-NS have been discovered on large self-transmissible plasmids, introducing a new dimension in considerations of the roles of H-NS-like proteins in horizontal gene transfer. Importantly, analogues of H-NS are now being discovered and characterized in Gram-negative bacteria such as Pseudomonas that are only distantly related to E. coli, in the medically important actinomycete Mycobacterium tuberculosis and even in Gram-positive organisms such as Bacillus subtilis.

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from Karlijn C. Bastiaansen, Wilbert Bitter and María A. Llamas writing in Bacterial Regulatory Networks:

Gene expression in bacteria is mainly controlled at the level of transcription initiation. To achieve this process a number of different mechanisms have evolved, one of which is the utilization of alternative sigma factors. Sigma factors are small proteins that associate with the RNA polymerase core enzyme (RNAPc) and direct it to specific promoter sequences, where they initiate gene transcription. Bacteria are able to regulate transcription initiation by synthesizing and activating different sigma factors that recognize different promoter consensus sequences. The largest group of alternative sigma factors consists of the so-called extracytoplasmic function (ECF) sigma factors that regulate gene expression in response to cell envelope stresses or environmental stimuli. The activity of ECF sigma factors is controlled by anti-sigma factors and a complex cascade of regulated (proteolytic) modifications. In gram-negative bacteria, ECF sigma factors are also controlled by cell-surface signalling (CSS), a regulatory system that includes an outer membrane receptor in the signal transduction pathway. In this chapter we will discuss the general composition and function of ECF sigma factors and their role in cell envelope stress responses and CSS.

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from J. Maxwell Dow, Yvonne McCarthy, Karen O'Donovan, Delphine Caly and Robert P. Ryan writing in Bacterial Regulatory Networks:

Cyclic di-GMP is now recognised as an almost universal second messenger in eubacteria that acts to regulate a wide range of functions including developmental transitions, adhesion, biofilm formation, motility and the synthesis of virulence factors. Cyclic di-GMP is synthesised from two GTP molecules by diguanylate cyclases that have a GGDEF domain and degraded by phosphodiesterases with either an EAL or HD-GYP domain. These proteins often have associated signal input domains, suggesting that their enzymatic activity may be modulated by different environmental or cellular cues. Cyclic di-GMP exerts a regulatory action through binding to diverse receptors that include a small protein domain called PilZ, transcription factors, enzymatically-inactive GGDEF, EAL or HD-GYP domains and riboswitches. The multiplicity of GGDEF, EAL and HD-GYP proteins together with a range of receptors within the same bacterial cell indicates the considerable complexity of cyclic di-GMP signalling. This has led to the concept of discrete pools of the nucleotide that are generated locally and act to influence intimately associated targets. A number of signalling proteins may be organised in a regulatory network to control a common function(s). Understanding cyclic di-GMP signalling may afford strategies for inhibition of biofilm formation and virulence factor synthesis in bacterial pathogens.

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from Patricia C. Burrows, Simone C. Wiesler, Zhensheng Pan, Martin Buck and Sivaramesh Wigneshweraraj writing in Bacterial Regulatory Networks:

Amongst the many accessory factors that bind RNA polymerase (RNAp) and serve to control its activities, sigma (σ) factors ubiquitously feature in programming of gene expression in response to abiotic and biotic cues. Here we review the role of the major variant σ factor, σ⁵⁴, in the expression of gene sets used for establishing the virulence of a wide range of pathogenic bacteria. The tight coupling of σ⁵⁴-dependent transcription to signalling pathways underpins the regulation of such systems, and allows a wide dynamic range of gene expression.

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from Kathryn A. Scott, Elizabeth E. Jefferys, Benjamin A. Hall, Mark A. J. Roberts and Judith P. Armitage writing in Bacterial Regulatory Networks:

Chemotaxis is the process by which bacteria migrate towards environments that are favourable for growth. Changes in the concentration of attractants or repellents are detected by receptors, which are usually transmembrane proteins. These receptors transduce the signal to the interior of the cell where a two-component system ultimately leads to changes in motile behaviour. Chemotaxis emerged as a beneficial trait for survival early in the evolution of bacteria and archaea. A core set of proteins is common to the chemosensory networks in many different species. During the evolution of bacteria this core network has diversified and expanded. Here we describe the conserved apparatus in the steps necessary for chemotaxis; sensing of chemoeffectors, signalling to the motility apparatus, rapid signal termination, and adaptation. We then highlight examples from species with complex chemosensory networks to illustrate the variations in chemotactic apparatus that have arisen from the common core.

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