Histidine kinases in signal transduction pathways of eukaryotes

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.

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Systematic Inactivation and Phenotypic Characterization of Two-Component Signal Transduction Systems of Enterococcus faecalis V583

Journal of Bacteriology ◽

10.1128/jb.186.23.7951-7958.2004 ◽

2004 ◽

Vol 186 (23) ◽

pp. 7951-7958 ◽

Cited By ~ 103

Author(s):

Lynn E. Hancock ◽

Marta Perego

Keyword(s):

Signal Transduction ◽

Antibiotic Resistance ◽

Environmental Stress ◽

Enterococcus Faecalis ◽

Response Regulator ◽

Phenotypic Characterization ◽

Response Regulators ◽

Two Component ◽

Two Component Signal Transduction ◽

Biofilm Development

ABSTRACT The ability of enterococci to adapt and respond to different environmental stimuli, including the host environment, led us to investigate the role of two-component signal transduction in the regulation of Enterococcus faecalis physiology. Using a bioinformatic approach, we previously identified 17 two-component systems (TCS), consisting of a sensory histidine kinase and the cognate response regulator, as well as an additional orphan response regulator (L. E. Hancock and M. Perego, J. Bacteriol. 184:5819-5825, 2002). In an effort to identify the potential function of each TCS in the biology of E. faecalis clinical isolate strain V583, we constructed insertion mutations in each of the response regulators. We were able to inactivate 17 of 18 response regulators, the exception being an ortholog of YycF, previously shown to be essential for viability in a variety of gram-positive microorganisms. The biological effects of the remaining mutations were assessed by using a number of assays, including antibiotic resistance, biofilm formation, and environmental stress. We identified TCS related to antibiotic resistance and environmental stress and found one system which controls the initiation of biofilm development by E. faecalis.

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

Journal of Bacteriology ◽

10.1128/jb.182.5.1423-1426.2000 ◽

2000 ◽

Vol 182 (5) ◽

pp. 1423-1426 ◽

Cited By ~ 32

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.

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A Selective Tether Recruits Activated Response Regulator CheB to Its Chemoreceptor Substrate

mBio ◽

10.1128/mbio.03106-21 ◽

2021 ◽

Author(s):

Mingshan Li ◽

Xianjin Xu ◽

Xiaoqin Zou ◽

Gerald L. Hazelbauer

Keyword(s):

Signal Transduction ◽

Response Regulator ◽

Response Regulators ◽

Two Component ◽

Primary Means ◽

Two Component Signal Transduction ◽

Sense And Respond ◽

Signal Transduction Systems

Two-component signal transduction systems are a primary means by which bacteria sense and respond to their environment. Response regulators are key components of these systems.

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Phyletic Distribution and Lineage-Specific Domain Architectures of Archaeal Two-Component Signal Transduction Systems

Journal of Bacteriology ◽

10.1128/jb.00681-17 ◽

2017 ◽

Vol 200 (7) ◽

Cited By ~ 8

Author(s):

Michael Y. Galperin ◽

Kira S. Makarova ◽

Yuri I. Wolf ◽

Eugene V. Koonin

Keyword(s):

Signal Transduction ◽

Protein Interactions ◽

Environmental Changes ◽

Metagenomic Data ◽

Protein Protein Interactions ◽

Response Regulators ◽

Histidine Kinases ◽

Content Type ◽

Two Component ◽

Two Component Signal Transduction

ABSTRACTThe two-component signal transduction (TCS) machinery is a key mechanism of sensing environmental changes in the prokaryotic world. TCS systems have been characterized thoroughly in bacteria but to a much lesser extent in archaea. Here, we provide an updated census of more than 2,000 histidine kinases and response regulators encoded in 218 complete archaeal genomes, as well as unfinished genomes available from metagenomic data. We describe the domain architectures of the archaeal TCS components, including several novel output domains, and discuss the evolution of the archaeal TCS machinery. The distribution of TCS systems in archaea is strongly biased, with high levels of abundance in haloarchaea and thaumarchaea but none detected in the sequenced genomes from the phylaCrenarchaeota,Nanoarchaeota, andKorarchaeota. The archaeal sensor histidine kinases are generally similar to their well-studied bacterial counterparts but are often located in the cytoplasm and carry multiple PAS and/or GAF domains. In contrast, archaeal response regulators differ dramatically from the bacterial ones. Most archaeal genomes do not encode any of the major classes of bacterial response regulators, such as the DNA-binding transcriptional regulators of the OmpR/PhoB, NarL/FixJ, NtrC, AgrA/LytR, and ActR/PrrA families and the response regulators with GGDEF and/or EAL output domains. Instead, archaea encode multiple copies of response regulators containing either the stand-alone receiver (REC) domain or combinations of REC with PAS and/or GAF domains. Therefore, the prevailing mechanism of archaeal TCS signaling appears to be via a variety of protein-protein interactions, rather than direct transcriptional regulation.IMPORTANCEAlthough theArchaearepresent a separate domain of life, their signaling systems have been assumed to be closely similar to the bacterial ones. A study of the domain architectures of the archaeal two-component signal transduction (TCS) machinery revealed an overall similarity of archaeal and bacterial sensory modules but substantial differences in the signal output modules. The prevailing mechanism of archaeal TCS signaling appears to involve various protein-protein interactions rather than direct transcription regulation. The complete list of histidine kinases and response regulators encoded in the analyzed archaeal genomes is available online athttp://www.ncbi.nlm.nih.gov/Complete_Genomes/TCSarchaea.html.

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

Microbiology ◽

10.1099/mic.0.29137-0 ◽

2006 ◽

Vol 152 (10) ◽

pp. 3035-3048 ◽

Cited By ~ 37

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.

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FixJ family regulator AcfR of Azorhizobium caulinodans is involved in symbiosis with the host plant

BMC Microbiology ◽

10.1186/s12866-021-02138-w ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Wei Liu ◽

Xue Bai ◽

Yan Li ◽

Haikun Zhang ◽

Xiaoke Hu

Keyword(s):

Signal Transduction ◽

Host Plant ◽

Type Strain ◽

Wild Type Strain ◽

Response Regulator ◽

Azorhizobium Caulinodans ◽

Wild Type ◽

Response Regulators ◽

Free Living ◽

Two Component

Abstract Background A wide variety of bacterial adaptative responses to environmental conditions are mediated by signal transduction pathways. Two-component signal transduction systems are one of the predominant means used by bacteria to sense the signals of the host plant and adjust their interaction behaviour. A total of seven open reading frames have been identified as putative two-component response regulators in the gram-negative nitrogen-fixing bacteria Azorhizobium caulinodans ORS571. However, the biological functions of these response regulators in the symbiotic interactions between A. caulinodans ORS571 and the host plant Sesbania rostrata have not been elucidated to date. Results In this study, we identified and investigated a two-component response regulator, AcfR, with a phosphorylatable N-terminal REC (receiver) domain and a C-terminal HTH (helix-turn-helix) LuxR DNA-binding domain in A. caulinodans ORS571. Phylogenetic analysis showed that AcfR possessed close evolutionary relationships with NarL/FixJ family regulators. In addition, six histidine kinases containing HATPase_c and HisKA domains were predicted to interact with AcfR. Furthermore, the biological function of AcfR in free-living and symbiotic conditions was elucidated by comparing the wild-type strain and the ΔacfR mutant strain. In the free-living state, the cell motility behaviour and exopolysaccharide production of the ΔacfR mutant were significantly reduced compared to those of the wild-type strain. In the symbiotic state, the ΔacfR mutant showed a competitive nodule defect on the stems and roots of the host plant, suggesting that AcfR can provide A. caulinodans with an effective competitive ability for symbiotic nodulation. Conclusions Our results showed that AcfR, as a response regulator, regulates numerous phenotypes of A. caulinodans under the free-living conditions and in symbiosis with the host plant. The results of this study help to elucidate the involvement of a REC + HTH_LuxR two-component response regulator in the Rhizobium-host plant interaction.

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-Lactam resistance modulated by the overexpression of response regulators of two-component signal transduction systems in Escherichia coli

Journal of Antimicrobial Chemotherapy ◽

10.1093/jac/dkg406 ◽

2003 ◽

Vol 52 (4) ◽

pp. 576-582 ◽

Cited By ~ 71

Author(s):

H. Hirakawa

Keyword(s):

Escherichia Coli ◽

Signal Transduction ◽

Response Regulators ◽

Two Component ◽

Two Component Signal Transduction ◽

Signal Transduction Systems

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

Journal of Bacteriology ◽

10.1128/jb.00139-17 ◽

2017 ◽

Vol 199 (18) ◽

Cited By ~ 15

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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