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

2017 ◽  
Vol 200 (7) ◽  
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.

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 Two-Component Signal Transduction Systems in the Human Pathogen Streptococcus agalactiae

2020 ◽  
Vol 88 (7) ◽  
Author(s):  
Lamar Thomas ◽  
Laura Cook
Keyword(s):  
Signal Transduction ◽  
Streptococcus Agalactiae ◽  
Metabolic Regulation ◽  
Invasive Infection ◽  
Older Individuals ◽  
Content Type ◽  
Two Component ◽  
Two Component Signal Transduction ◽  
Group B ◽  
Signal Transduction Systems

ABSTRACT Streptococcus agalactiae (group B Streptococcus [GBS]) is an important cause of invasive infection in newborns, maternal women, and older individuals with underlying chronic illnesses. GBS has many mechanisms to adapt and survive in its host, and these mechanisms are often controlled via two-component signal transduction systems. In GBS, more than 20 distinct two-component systems (TCSs) have been classified to date, consisting of canonical TCSs as well as orphan and atypical sensors and regulators. These signal transducing systems are necessary for metabolic regulation, resistance to antibiotics and antimicrobials, pathogenesis, and adhesion to the mucosal surfaces to colonize the host. This minireview discusses the structures of these TCSs in GBS as well as how selected systems regulate essential cellular processes such as survival and colonization. GBS contains almost double the number of TCSs compared to the closely related Streptococcus pyogenes and Streptococcus pneumoniae, and while research on GBS TCSs has been increasing in recent years, no comprehensive reviews of these TCSs exist, making this review especially relevant.

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.

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

2004 ◽  
Vol 186 (23) ◽  
pp. 7951-7958 ◽  
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.

scholarly journals The ChrSA and HrrSA Two-Component Systems Are Required for Transcriptional Regulation of thehemAPromoter in Corynebacterium diphtheriae

2016 ◽  
Vol 198 (18) ◽  
pp. 2419-2430 ◽  
Author(s):  
Jonathan M. Burgos ◽  
Michael P. Schmitt
Keyword(s):  
Signal Transduction ◽  
Kinase Activity ◽  
Content Type ◽  
Component Systems ◽  
Two Component ◽  
Two Component Signal Transduction ◽  
Two Component Systems ◽  
Signal Transduction Systems

ABSTRACTCorynebacterium diphtheriaeutilizes heme and hemoglobin (Hb) as iron sources for growth in low-iron environments. InC. diphtheriae, the two-component signal transduction systems (TCSs) ChrSA and HrrSA are responsive to Hb levels and regulate the transcription of promoters forhmuO,hrtAB, andhemA. ChrSA and HrrSA activate transcription at thehmuOpromoter and repress transcription athemAin an Hb-dependent manner. In this study, we show that HrrSA is the predominant repressor athemAand that its activity results in transcriptional repression in the presence and absence of Hb, whereas repression ofhemAby ChrSA is primarily responsive to Hb. DNA binding studies showed that both ChrA and HrrA bind to thehemApromoter region at virtually identical sequences. ChrA binding was enhanced by phosphorylation, while binding to DNA by HrrA was independent of its phosphorylation state. ChrA and HrrA are phosphorylatedin vitroby the sensor kinase ChrS, whereas no kinase activity was observed with HrrSin vitro. Phosphorylated ChrA was not observedin vivo, even in the presence of Hb, which is likely due to the instability of the phosphate moiety on ChrA. However, phosphorylation of HrrA was observedin vivoregardless of the presence of the Hb inducer, and genetic analysis indicates that ChrS is responsible for most of the phosphorylation of HrrAin vivo. Phosphorylation studies strongly suggest that HrrS functions primarily as a phosphatase and has only minimal kinase activity. These findings collectively show a complex mechanism of regulation at thehemApromoter, where both two-component systems act in concert to optimize expression of heme biosynthetic enzymes.IMPORTANCEUnderstanding the mechanism by which two-component signal transduction systems function to respond to environmental stimuli is critical to the study of bacterial pathogenesis. The current study expands on the previous analyses of the ChrSA and HrrSA TCSs in the human pathogenC. diphtheriae. The findings here underscore the complex interactions between the ChrSA and HrrSA systems in the regulation of thehemApromoter and demonstrate how the two systems complement one another to refine and control transcription in the presence and absence of Hb.

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 Development and Validation of a High-Throughput Cell-Based Screen To Identify Activators of a Bacterial Two-Component Signal Transduction System

2015 ◽  
Vol 59 (7) ◽  
pp. 3789-3799 ◽  
Author(s):  
Julia J. van Rensburg ◽  
Kate R. Fortney ◽  
Lan Chen ◽  
Andrew J. Krieger ◽  
Bruno P. Lima ◽  
...  
Keyword(s):  
Signal Transduction ◽  
High Throughput ◽  
Response Regulator ◽  
Phosphoryl Group ◽  
Signal Transduction System ◽  
Membrane Repair ◽  
Content Type ◽  
Two Component ◽  
Serovar Typhimurium ◽  
Two Component Signal Transduction

ABSTRACTCpxRA is a two-component signal transduction system (2CSTS) found in many drug-resistant Gram-negative bacteria. In response to periplasmic stress, CpxA autophosphorylates and donates a phosphoryl group to its cognate response regulator, CpxR. Phosphorylated CpxR (CpxR-P) upregulates genes involved in membrane repair and downregulates multiple genes that encode virulence factors, which are trafficked across the cell membrane. Mutants that constitutively activate CpxRA inSalmonella entericaserovar Typhimurium andHaemophilus ducreyiare avirulent in mice and humans, respectively. Thus, the activation of CpxRA has high potential as a novel antimicrobial/antivirulence strategy. Using a series ofEscherichia colistrains containing a CpxR-P-responsivelacZreporter and deletions in genes encoding CpxRA system components, we developed and validated a novel cell-based high-throughput screen (HTS) for CpxRA activators. A screen of 36,000 compounds yielded one hit compound that increased reporter activity in wild-type cells. This is the first report of a compound that activates, rather than inhibits, a 2CSTS. The activity profile of the compound against CpxRA pathway mutants in the presence of glucose suggested that the compound inhibits CpxA phosphatase activity. We confirmed that the compound induced the accumulation of CpxR-P in treated cells. Although the hit compound contained a nitro group, a derivative lacking this group retained activity in serum and had lower cytotoxicity than that of the initial hit. This HTS is amenable for the screening of larger libraries to find compounds that activate CpxRA by other mechanisms, and it could be adapted to find activators of other two-component systems.

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