scholarly journals Effects of the Global Regulator CsrA on the BarA/UvrY Two-Component Signaling System

2014 ◽  
Vol 197 (5) ◽  
pp. 983-991 ◽  
Author(s):  
Martha I. Camacho ◽  
Adrian F. Alvarez ◽  
Ricardo Gonzalez Chavez ◽  
Tony Romeo ◽  
Enrique Merino ◽  
...  
Keyword(s):  
Small Rnas ◽  
Feedback Loop ◽  
Kinase Activity ◽  
Rna Binding ◽  
Response Regulator ◽  
Global Regulator ◽  
Regulatory Systems ◽  
Two Component ◽  
Two Component Signal Transduction ◽  
Cognate Response Regulator

The hybrid sensor kinase BarA and its cognate response regulator UvrY, members of the two-component signal transduction family, activate transcription of CsrB and CsrC noncoding RNAs. These two small RNAs act by sequestering the RNA binding protein CsrA, which posttranscriptionally regulates translation and/or stability of its target mRNAs. Here, we provide evidence that CsrA positively affects, although indirectly,uvrYexpression, at both the transcriptional and translational levels. We also demonstrate that CsrA is required for properly switching BarA from its phosphatase to its kinase activity. Thus, the existence of a feedback loop mechanism that involves the Csr and BarA/UvrY global regulatory systems is exposed.

scholarly journals The Two-Component Regulatory System TCS08 Is Involved in Cellobiose Metabolism of Streptococcus pneumoniae R6

2006 ◽  
Vol 189 (4) ◽  
pp. 1342-1350 ◽  
Author(s):  
Stuart J. McKessar ◽  
Regine Hakenbeck
Keyword(s):  
Streptococcus Pneumoniae ◽  
Response Regulator ◽  
Regulatory System ◽  
Phosphotransferase System ◽  
Two Component System ◽  
Transcription Profiles ◽  
Regulatory Systems ◽  
Two Component ◽  
Cognate Response Regulator ◽  
Gram Positive Cocci

ABSTRACT The two-component system TCS08 is one of the regulatory systems that is important for virulence of Streptococcus pneumoniae. In order to investigate the TCS08 regulon, we have analyzed transcription profiles of mutants derived from S. pneumoniae R6 by microarray analysis. Since deletion mutants are often without a significant phenotype, we constructed a mutation in the histidine kinase HK08, T133P, in analogy to the phosphatase mutation T230P in the H box of the S. pneumoniae CiaH kinase described recently (D. Zähner, K. Kaminski, M. van der Linden, T. Mascher, M. Merai, and R. Hakenbeck, J. Mol. Microbiol. Biotechnol. 4:211-216, 2002). In addition, a deletion mutation was constructed in rr08, encoding the cognate response regulator. The most heavily suppressed genes in the hk08 mutant were spr0276 to spr0282, encoding a putative cellobiose phosphoenolpyruvate sugar phosphotransferase system (PTS). Whereas the R6 Smr parent strain and the Δrr08 mutant readily grew on cellobiose, the hk08 mutant and selected mutants with deletions in the PTS cluster did not, strongly suggesting that TCS08 is involved in the catabolism of cellobiose. Homologues of the TCS08 system were found in closely related streptococci and other gram-positive cocci. However, the genes spr0276 to spr0282, encoding the putative cellobiose PTS, represent a genomic island in S. pneumoniae and homologues were found in Streptococcus gordonii only, suggesting that this system might contribute to the pathogenicity potential of the pneumococcus.

scholarly journals Cpx Two-Component Signal Transduction inEscherichia coli: Excessive CpxR-P Levels Underlie CpxA* Phenotypes

2000 ◽  
Vol 182 (5) ◽  
pp. 1423-1426 ◽  
Author(s):  
Peter De Wulf ◽  
E. C. C. Lin
Keyword(s):  
Signal Transduction ◽  
Response Regulator ◽  
Response Regulators ◽  
Signal Transduction System ◽  
Regulate Gene Expression ◽  
Adverse Conditions ◽  
Two Component ◽  
Sensor Protein ◽  
Two Component Signal Transduction ◽  
Cognate Response Regulator

ABSTRACT In Escherichia coli, the CpxA-CpxR two-component signal transduction system and the ςE and ς32response pathways jointly regulate gene expression in adaptation to adverse conditions. These include envelope protein distress, heat shock, oxidative stress, high pH, and entry into stationary phase. Certain mutant versions of the CpxA sensor protein (CpxA* proteins) exhibit an elevated ratio of kinase to phosphatase activity on CpxR, the cognate response regulator. As a result, CpxA* strains display numerous phenotypes, many of which cannot be easily related to currently known functions of the CpxA-CpxR pathway. It is unclear whether CpxA* phenotypes are caused solely by hyperphosphorylation of CpxR. We here report that all of the tested CpxA* phenotypes depend on elevated levels of CpxR-P and not on cross-signalling of CpxA* to noncognate response regulators.

scholarly journals Comparative analysis of two-component signal transduction systems of Bacillus cereus, Bacillus thuringiensis and Bacillus anthracis

Microbiology ◽  
2006 ◽  
Vol 152 (10) ◽  
pp. 3035-3048 ◽  
Author(s):  
Mark de Been ◽  
Christof Francke ◽  
Roy Moezelaar ◽  
Tjakko Abee ◽  
Roland J. Siezen
Keyword(s):  
Signal Transduction ◽  
Bacillus Cereus ◽  
Response Regulator ◽  
Adaptive Responses ◽  
Wide Range ◽  
Two Component ◽  
Two Component Signal Transduction ◽  
Host Microbe Interactions ◽  
Cognate Response Regulator ◽  
Signal Transduction Systems

Members of the Bacillus cereus group are ubiquitously present in the environment and can adapt to a wide range of environmental fluctuations. In bacteria, these adaptive responses are generally mediated by two-component signal transduction systems (TCSs), which consist of a histidine kinase (HK) and its cognate response regulator (RR). With the use of in silico techniques, a complete set of HKs and RRs was recovered from eight completely sequenced B. cereus group genomes. By applying a bidirectional best-hits method combined with gene neighbourhood analysis, a footprint of these proteins was made. Around 40 HK-RR gene pairs were detected in each member of the B. cereus group. In addition, each member contained many HK and RR genes not encoded in pairs (‘orphans’). Classification of HKs and RRs based on their enzymic domains together with the analysis of two neighbour-joining trees of these domains revealed putative interaction partners for most of the ‘orphans’. Putative biological functions, including involvement in virulence and host–microbe interactions, were predicted for the B. cereus group HKs and RRs by comparing them with those of B. subtilis and other micro-organisms. Remarkably, B. anthracis appeared to lack specific HKs and RRs and was found to contain many truncated, putatively non-functional, HK and RR genes. It is hypothesized that specialization of B. anthracis as a pathogen could have reduced the range of environmental stimuli to which it is exposed. This may have rendered some of its TCSs obsolete, ultimately resulting in the deletion of some HK and RR genes.

scholarly journals Evolution of two-component quorum sensing systems

2022 ◽  
Vol 4 (1) ◽  
Author(s):  
Marina Giannakara ◽  
Vassiliki Lila Koumandou
Keyword(s):  
Quorum Sensing ◽  
Response Regulator ◽  
Phylogenetic Analyses ◽  
Cell Communication ◽  
Evolutionary Relationships ◽  
Response Regulators ◽  
Modular Architecture ◽  
Two Component ◽  
Two Component Signal Transduction ◽  
Cognate Response Regulator

Quorum sensing (QS) is a cell-to-cell communication system that enables bacteria to coordinate their gene expression depending on their population density, via the detection of small molecules called autoinducers. In this way bacteria can act collectively to initiate processes like bioluminescence, virulence and biofilm formation. Autoinducers are detected by receptors, some of which are part of two-component signal transduction systems (TCS), which comprise of a (usually membrane-bound) sensor histidine kinase (HK) and a cognate response regulator (RR). Different QS systems are used by different bacterial taxa, and their relative evolutionary relationships have not been extensively studied. To address this, we used the Kyoto Encyclopedia of Genes and Genomes (KEGG) database to identify all the QS HKs and RRs that are part of TCSs and examined their conservation across microbial taxa. We compared the combinations of the highly conserved domains in the different families of receptors and response regulators using the Simple Modular Architecture Research Tool (SMART) and KEGG databases, and we also carried out phylogenetic analyses for each family, and all families together. The distribution of the different QS systems across taxa, indicates flexibility in HK–RR pairing and highlights the need for further study of the most abundant systems. For both the QS receptors and the response regulators, our results indicate close evolutionary relationships between certain families, highlighting a common evolutionary history which can inform future applications, such as the design of novel inhibitors for pathogenic QS systems.

Histidine kinases in signal transduction pathways of eukaryotes

1997 ◽  
Vol 110 (10) ◽  
pp. 1141-1145 ◽  
Author(s):  
W.F. Loomis ◽  
G. Shaulsky ◽  
N. Wang
Keyword(s):  
Signal Transduction ◽  
Response Regulator ◽  
Signal Transduction Pathways ◽  
Response Regulators ◽  
Histidine Kinases ◽  
Camp Phosphodiesterase ◽  
Wide Range ◽  
Two Component ◽  
Two Component Signal Transduction ◽  
Dependent Protein

Autophosphorylating histidine kinases are an ancient conserved family of enzymes that are found in eubacteria, archaebacteria and eukaryotes. They are activated by a wide range of extracellular signals and transfer phosphate moieties to aspartates found in response regulators. Recent studies have shown that such two-component signal transduction pathways mediate osmoregulation in Saccharomyces cerevisiae, Dictyostelium discoideum and Neurospora crassa. Moreover, they play pivotal roles in responses of Arabidopsis thaliana to ethylene and cytokinin. A transmembrane histidine kinase encoded by dhkA accumulates when Dictyostelium cells aggregate during development. Activation of DhkA results in the inhibition of its response regulator, RegA, which is a cAMP phosphodiesterase that regulates the cAMP dependent protein kinase PKA. When PKA is activated late in the differentiation of prespore cells, they encapsulate into spores. There is evidence that this two-component system participates in a feedback loop linked to PKA in prestalk cells such that the signal to initiate encapsulation is rapidly amplified. Such signal transduction pathways can be expected to be found in a variety of eukaryotic differentiations since they are rapidly reversible and can integrate disparate signals.

scholarly journals Progress Overview of Bacterial Two-Component Regulatory Systems as Potential Targets for Antimicrobial Chemotherapy

Antibiotics ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 635
Author(s):  
Hidetada Hirakawa ◽  
Jun Kurushima ◽  
Yusuke Hashimoto ◽  
Haruyoshi Tomita
Keyword(s):  
Drug Resistance ◽  
Antimicrobial Chemotherapy ◽  
Response Regulator ◽  
Regulatory System ◽  
Laboratory Strain ◽  
Regulatory Systems ◽  
Two Component ◽  
Bacterial Genes ◽  
Conventional Antibiotics ◽  
External Stimuli

Bacteria adapt to changes in their environment using a mechanism known as the two-component regulatory system (TCS) (also called “two-component signal transduction system” or “two-component system”). It comprises a pair of at least two proteins, namely the sensor kinase and the response regulator. The former senses external stimuli while the latter alters the expression profile of bacterial genes for survival and adaptation. Although the first TCS was discovered and characterized in a non-pathogenic laboratory strain of Escherichia coli, it has been recognized that all bacteria, including pathogens, use this mechanism. Some TCSs are essential for cell growth and fitness, while others are associated with the induction of virulence and drug resistance/tolerance. Therefore, the TCS is proposed as a potential target for antimicrobial chemotherapy. This concept is based on the inhibition of bacterial growth with the substances acting like conventional antibiotics in some cases. Alternatively, TCS targeting may reduce the burden of bacterial virulence and drug resistance/tolerance, without causing cell death. Therefore, this approach may aid in the development of antimicrobial therapeutic strategies for refractory infections caused by multi-drug resistant (MDR) pathogens. Herein, we review the progress of TCS inhibitors based on natural and synthetic compounds.

scholarly journals Functional reconstitution of the Salmonella typhimurium PhoQ histidine kinase sensor in proteoliposomes

2005 ◽  
Vol 390 (3) ◽  
pp. 769-776 ◽  
Author(s):  
Sarah Sanowar ◽  
Hervé Le Moual
Keyword(s):  
Salmonella Typhimurium ◽  
Histidine Kinase ◽  
Catalytic Domain ◽  
Response Regulator ◽  
Phosphoryl Group ◽  
Two Component ◽  
Two Component Signal Transduction ◽  
High Concentrations

Two-component signal-transduction systems are widespread in bacteria. They are usually composed of a transmembrane histidine kinase sensor and a cytoplasmic response regulator. The PhoP/PhoQ two-component system of Salmonella typhimurium contributes to virulence by co-ordinating the adaptation to low concentrations of environmental Mg2+. Limiting concentrations of extracellular Mg2+ activate the PhoP/PhoQ phosphorylation cascade modulating the transcription of PhoP-regulated genes. In contrast, high concentrations of extracellular Mg2+ stimulate the dephosphorylation of the response regulator PhoP by the PhoQ kinase sensor. In the present study, we report the purification and functional reconstitution of PhoQHis, a PhoQ variant with a C-terminal His tag, into Escherichia coli liposomes. The functionality of PhoQHis was essentially similar to that of PhoQ as shown in vivo and in vitro. Purified PhoQHis was inserted into liposomes in a unidirectional orientation, with the sensory domain facing the lumen and the catalytic domain facing the extraluminal environment. Reconstituted PhoQHis exhibited all the catalytic activities that have been described for histidine kinase sensors. Reconstituted PhoQHis was capable of autokinase activity when incubated in the presence of Mg2+-ATP. The phosphoryl group could be transferred from reconstituted PhoQHis to PhoP. Reconstituted PhoQHis catalysed the dephosphorylation of phospho-PhoP and this activity was stimulated by the addition of extraluminal ADP.

scholarly journals Crystal Structure of the Response Regulator 02 Receiver Domain, the Essential YycF Two-Component System of Streptococcus pneumoniae in both Complexed and Native States

2004 ◽  
Vol 186 (9) ◽  
pp. 2872-2879 ◽  
Author(s):  
Colin J. Bent ◽  
Neil W. Isaacs ◽  
Timothy J. Mitchell ◽  
Alan Riboldi-Tunnicliffe
Keyword(s):  
Streptococcus Pneumoniae ◽  
Active Site ◽  
Response Regulator ◽  
Thermotoga Maritima ◽  
Two Component System ◽  
Environmental Signals ◽  
Receiver Domain ◽  
Two Component ◽  
Protein Sequence Homology ◽  
Two Component Signal Transduction

ABSTRACT A variety of bacterial cellular responses to environmental signals are mediated by two-component signal transduction systems comprising a membrane-associated histidine protein kinase and a cytoplasmic response regulator (RR), which interpret specific stimuli and produce a measured physiological response. In RR activation, transient phosphorylation of a highly conserved aspartic acid residue drives the conformation changes needed for full activation of the protein. Sequence homology reveals that RR02 from Streptococcus pneumoniae belongs to the OmpR subfamily of RRs. The structures of the receiver domains from four members of this family, DrrB and DrrD from Thermotoga maritima, PhoB from Escherichia coli, and PhoP from Bacillus subtilis, have been elucidated. These domains are globally very similar in that they are composed of a doubly wound α5β5; however, they differ remarkably in the fine detail of the β4-α4 and α4 regions. The structures presented here reveal a further difference of the geometry in this region. RR02 is has been shown to be the essential RR in the gram-positive bacterium S. pneumoniae R. Lange, C. Wagner, A. de Saizieu, N. Flint, J. Molnos, M. Stieger, P. Caspers, M. Kamber, W. Keck, and K. E. Amrein, Gene 237:223-234, 1999; J. P. Throup, K. K. Koretke, A. P. Bryant, K. A. Ingraham, A. F. Chalker, Y. Ge, A. Marra, N. G. Wallis, J. R. Brown, D. J. Holmes, M. Rosenberg, and M. K. Burnham, Mol. Microbiol. 35:566-576, 2000). RR02 functions as part of a phosphotransfer system that ultimately controls the levels of competence within the bacteria. Here we report the native structure of the receiver domain of RR02 from serotype 4 S. pneumoniae (as well as acetate- and phosphate-bound forms) at different pH levels. Two native structures at 2.3 Å, phased by single-wavelength anomalous diffraction (xenon SAD), and 1.85 Å and a third structure at pH 5.9 revealed the presence of a phosphate ion outside the active site. The fourth structure revealed the presence of an acetate molecule in the active site.

scholarly journals The Two-Component Signal Transduction System VxrAB Positively Regulates Vibrio cholerae Biofilm Formation

2017 ◽  
Vol 199 (18) ◽  
Author(s):  
Jennifer K. Teschler ◽  
Andrew T. Cheng ◽  
Fitnat H. Yildiz
Keyword(s):  
Signal Transduction ◽  
Vibrio Cholerae ◽  
Histidine Kinase ◽  
Biofilm Formation ◽  
Pathogenic Bacteria ◽  
Response Regulator ◽  
Systematic Analysis ◽  
Content Type ◽  
Two Component ◽  
Two Component Signal Transduction

ABSTRACT Two-component signal transduction systems (TCSs), typically composed of a sensor histidine kinase (HK) and a response regulator (RR), are the primary mechanism by which pathogenic bacteria sense and respond to extracellular signals. The pathogenic bacterium Vibrio cholerae is no exception and harbors 52 RR genes. Using in-frame deletion mutants of each RR gene, we performed a systematic analysis of their role in V. cholerae biofilm formation. We determined that 7 RRs impacted the expression of an essential biofilm gene and found that the recently characterized RR, VxrB, regulates the expression of key structural and regulatory biofilm genes in V. cholerae. vxrB is part of a 5-gene operon, which contains the cognate HK vxrA and three genes of unknown function. Strains carrying ΔvxrA and ΔvxrB mutations are deficient in biofilm formation, while the ΔvxrC mutation enhances biofilm formation. The overexpression of VxrB led to a decrease in motility. We also observed a small but reproducible effect of the absence of VxrB on the levels of cyclic di-GMP (c-di-GMP). Our work reveals a new function for the Vxr TCS as a regulator of biofilm formation and suggests that this regulation may act through key biofilm regulators and the modulation of cellular c-di-GMP levels. IMPORTANCE Biofilms play an important role in the Vibrio cholerae life cycle, providing protection from environmental stresses and contributing to the transmission of V. cholerae to the human host. V. cholerae can utilize two-component systems (TCS), composed of a histidine kinase (HK) and a response regulator (RR), to regulate biofilm formation in response to external cues. We performed a systematic analysis of V. cholerae RRs and identified a new regulator of biofilm formation, VxrB. We demonstrated that the VxrAB TCS is essential for robust biofilm formation and that this system may regulate biofilm formation via its regulation of key biofilm regulators and cyclic di-GMP levels. This research furthers our understanding of the role that TCSs play in the regulation of V. cholerae biofilm formation.

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