scholarly journals Complexity in ?2-component? signal transduction systems

2006 ◽  
Vol 27 (3) ◽  
pp. 128
Author(s):  
Cynthia B Whitchurch
Keyword(s):  
Signal Transduction ◽  
Histidine Kinase ◽  
Environmental Changes ◽  
Response Regulator ◽  
Sensor Histidine Kinase ◽  
Regulatory Systems ◽  
Transduction Mechanisms ◽  
Membrane Bound ◽  
Signal Transduction Systems

The ?2-component? regulatory systems of bacteria are the predominant signal transduction mechanisms that bacteria utilise to modulate behaviours and metabolism in response to environmental changes. These systems classically involve two proteins ? a membrane bound sensor histidine kinase and a soluble response regulator.

scholarly journals ChiS is a noncanonical DNA-binding hybrid sensor kinase that directly regulates the chitin utilization program inVibrio cholerae

2020 ◽  
Vol 117 (33) ◽  
pp. 20180-20189 ◽  
Author(s):  
Catherine A. Klancher ◽  
Shouji Yamamoto ◽  
Triana N. Dalia ◽  
Ankur B. Dalia
Keyword(s):  
Gene Expression ◽  
Signal Transduction ◽  
Dna Binding ◽  
Histidine Kinase ◽  
Response Regulator ◽  
Bacterial Species ◽  
Dependent Manner ◽  
Major Mechanism ◽  
Sense And Respond ◽  
Signal Transduction Systems

Two-component signal transduction systems (TCSs) represent a major mechanism that bacteria use to sense and respond to their environment. Prototypical TCSs are composed of a membrane-embedded histidine kinase, which senses an environmental stimulus and subsequently phosphorylates a cognate partner protein called a response regulator that regulates gene expression in a phosphorylation-dependent manner.Vibrio choleraeuses the hybrid histidine kinase ChiS to activate the expression of the chitin utilization program, which is critical for the survival of this facultative pathogen in its aquatic reservoir. A cognate response regulator for ChiS has not been identified and the mechanism of ChiS-dependent signal transduction remains unclear. Here, we show that ChiS is a noncanonical membrane-embedded one-component system that can both sense chitin and directly regulate gene expression via a cryptic DNA binding domain. Unlike prototypical TCSs, we find that ChiS DNA binding is diminished, rather than stimulated, by phosphorylation. Finally, we provide evidence that ChiS likely activates gene expression by directly recruiting RNA polymerase. This work addresses the mechanism of action for a major transcription factor inV. choleraeand highlights the versatility of signal transduction systems in bacterial species.

scholarly journals Competence Modulation by the NADH Oxidase ofStreptococcus pneumoniae Involves Signal Transduction

2001 ◽  
Vol 183 (2) ◽  
pp. 768-772 ◽  
Author(s):  
José R. Echenique ◽  
Marie C. Trombe
Keyword(s):  
Signal Transduction ◽  
Transcriptional Activation ◽  
Transcriptional Control ◽  
Nadh Oxidase ◽  
Response Regulator ◽  
Transcriptional Analysis ◽  
Genetic Dissection ◽  
Oxygen Signaling ◽  
Two Component Signal Transduction ◽  
Signal Transduction Systems

ABSTRACT Oxygen controls competence development in Streptococcus pneumoniae. Oxygen signaling involves the two-component signal transduction systems CiaRH and ComDE and the competence-stimulating peptide encoded by comC and processed by ComAB. We found that NADH oxidase (Nox) was required for optimal competence. Transcriptional analysis and genetic dissection showed that Nox was involved in post-transcriptional activation of the response regulator ComE and in the transcriptional control of ciaRH andcomCDE. Thus, in S. pneumoniae, Nox, with O2 as its secondary substrate, is part of the O2-signaling pathway.

Kinetic and mechanistic analyses of new classes of inhibitors of two-component signal transduction systems using a coupled assay containing HpkA–DrrA from Thermotoga maritima

Microbiology ◽  
2004 ◽  
Vol 150 (4) ◽  
pp. 885-896 ◽  
Author(s):  
J. Estelle Foster ◽  
Qin Sheng ◽  
Jonathan R. McClain ◽  
Mark Bures ◽  
Thalia I. Nicas ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Histidine Kinase ◽  
Competitive Inhibition ◽  
Thermotoga Maritima ◽  
Phosphorylation Site ◽  
Phosphoryl Group ◽  
Two Component ◽  
Two Component Signal Transduction ◽  
Coupled Assay ◽  
Signal Transduction Systems

Two-component signal transduction systems (TCSs) play fundamental roles in bacterial survival and pathogenesis and have been proposed as targets for the development of novel classes of antibiotics. A new coupled assay was developed and applied to analyse the kinetic mechanisms of three new kinds of inhibitors of TCS function. The assay exploits the biochemical properties of the cognate HpkA–DrrA histidine kinase–response regulator pair from Thermotoga maritima and allows multiple turnovers of HpkA, linear formation of phosphorylated DrrA, and Michaelis–Menten analysis of inhibitors. The assay was validated in several ways, including confirmation of competitive inhibition by adenosine 5′-β,γ-imidotriphosphate (AMP-PNP). The coupled assay, autophosphorylation and chemical cross-linking were used to determine the mechanisms by which several compounds inhibit TCS function. A cyanoacetoacetamide showed non-competitive inhibition with respect to ATP concentration in the coupled assay. The cyanoacetoacetamide also inhibited autophosphorylation of histidine kinases from other bacteria, indicating that the coupled assay could detect general inhibitors of histidine kinase function. Inhibition of HpkA autophosphorylation by this compound was probably caused by aggregation of HpkA, consistent with a previous model for other hydrophobic compounds. In contrast, ethodin was a potent inhibitor of the combined assay, did not inhibit HpkA autophosphorylation, but still led to aggregation of HpkA. These data suggest that ethodin bound to the HpkA kinase and inhibited transfer of the phosphoryl group to DrrA. A peptide corresponding to the phosphorylation site of DrrA appeared to inhibit TCS function by a mechanism similar to that of ethodin, except that autophosphorylation was inhibited at high peptide concentrations. The latter mechanism of inhibition of TCS function is unusual and its analysis demonstrates the utility of these approaches to the kinetic analyses of additional new classes of inhibitors of TCS function.

scholarly journals Identification of Proteins Likely To Be Involved in Morphogenesis, Cell Division, and Signal Transduction in Planctomycetes by Comparative Genomics

2012 ◽  
Vol 194 (23) ◽  
pp. 6419-6430 ◽  
Author(s):  
Christian Jogler ◽  
Jost Waldmann ◽  
Xiaoluo Huang ◽  
Mareike Jogler ◽  
Frank Oliver Glöckner ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Cell Division ◽  
Model Organisms ◽  
Genetic Studies ◽  
Content Type ◽  
Life Styles ◽  
Membrane Bound ◽  
Guilt By Association ◽  
Complex Signaling ◽  
Signal Transduction Systems

ABSTRACTMembers of thePlanctomycetesclade share many unusual features for bacteria. Their cytoplasm contains membrane-bound compartments, they lack peptidoglycan and FtsZ, they divide by polar budding, and they are capable of endocytosis. Planctomycete genomes have remained enigmatic, generally being quite large (up to 9 Mb), and on average, 55% of their predicted proteins are of unknown function. Importantly, proteins related to the unusual traits ofPlanctomycetesremain largely unknown. Thus, we embarked on bioinformatic analyses of these genomes in an effort to predict proteins that are likely to be involved in compartmentalization, cell division, and signal transduction. We used three complementary strategies. First, we defined thePlanctomycetescore genome and subtracted genes of well-studied model organisms. Second, we analyzed the gene content and synteny of morphogenesis and cell division genes and combined both methods using a “guilt-by-association” approach. Third, we identified signal transduction systems as well as sigma factors. These analyses provide a manageable list of candidate genes for future genetic studies and provide evidence for complex signaling in thePlanctomycetesakin to that observed for bacteria with complex life-styles, such asMyxococcus xanthus.

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 Ethanolamine Activates a Sensor Histidine Kinase Regulating Its Utilization in Enterococcus faecalis

2008 ◽  
Vol 190 (21) ◽  
pp. 7147-7156 ◽  
Author(s):  
María Florencia Del Papa ◽  
Marta Perego
Keyword(s):  
Enterococcus Faecalis ◽  
Histidine Kinase ◽  
Intestinal Tract ◽  
Response Regulator ◽  
Synthetic Medium ◽  
Fold Increase ◽  
Ecological Niches ◽  
Bacterial Invasion ◽  
Sensor Histidine Kinase

ABSTRACT Enterococcus faecalis is a gram-positive commensal bacterium of the human intestinal tract. Its opportunistic pathogenicity has been enhanced by the acquisition of multiple antibiotic resistances, making the treatment of enterococcal infections an increasingly difficult problem. The extraordinary capacity of this organism to colonize and survive in a wide variety of ecological niches is attributable, at least in part, to signal transduction pathways mediated by two-component systems (TCS). Here, the ability of E. faecalis to utilize ethanolamine as the sole carbon source is shown to be dependent upon the RR-HK17 (EF1633-EF1632) TCS. Ethanolamine is an abundant compound in the human intestine, and thus, the ability of bacteria to utilize it as a source of carbon and nitrogen may provide an advantage for survival and colonization. Growth of E. faecalis in a synthetic medium with ethanolamine was abolished in the response regulator RR17 mutant strain. Transcription of the response regulator gene was induced by the presence of ethanolamine. Ethanolamine induced a 15-fold increase in the rate of autophosphorylation in vitro of the HK17 sensor histidine kinase, indicating that this is the ligand recognized by the sensor domain of the kinase. These results assign a role to the RR-HK17 TCS as coordinator of the enterococcal response to specific nutritional conditions existing at the site of bacterial invasion, the intestinal tract of an animal host.

scholarly journals A bacterial signal transduction phosphorelay in the methanogenic archaeon Methanosarcina acetivorans

2021 ◽  
Author(s):  
Nicole Frankenberg-Dinkel ◽  
Anne Sexauer
Keyword(s):  
Signal Transduction ◽  
Histidine Kinase ◽  
Environmental Changes ◽  
Methanosarcina Acetivorans ◽  
Histidine Kinases ◽  
C Terminus ◽  
Component Systems ◽  
Two Component Systems ◽  
Bacterial Type

Signal transduction via two-component systems is a powerful tool for microorganisms to respond to environmental changes. Histidine kinases originating from Bacteria are the most common signaling enzymes and are also present in Archaea, but not in all phyla. A total of 124 bacterial-type histidine kinases and/or regulators were identified in a screen of 149 Euryarchaeota genomes, but little is known about the signal transfer and molecular regulation of these systems. In this work, the hybrid kinase MA4377 from the methanogenic archaeon Methanosarcina acetivorans was investigated. MA4377 is a multidomain protein resembling a bacterial-type histidine kinase with two additional receiver domains at the C-terminus. Recombinant protein was employed to investigate the intra- and intermolecular phosphorelay in vitro. The kinase displays autophosphorylation activity of histidine residue 497. While no intramolecular phosphorelay was observed, the CheY-like receiver protein MA4376 was identified as part of the multi-component system that also seems to include the Msr-type transcription factor MA4375. This study reveals the presence and in vitro function of a bacterial-type hybrid histidine kinase integrated into an archaeal phosphorelay system.

scholarly journals Novel two-component regulatory systems play a role in biofilm formation of Lactobacillus reuteri rodent isolate 100-23

Microbiology ◽  
2014 ◽  
Vol 160 (4) ◽  
pp. 795-806 ◽  
Author(s):  
Marcia Shu-Wei Su ◽  
Michael G. Gänzle
Keyword(s):  
Histidine Kinase ◽  
Biofilm Formation ◽  
Lactobacillus Reuteri ◽  
Response Regulator ◽  
Multiple Genes ◽  
Regulatory Systems ◽  
Two Component ◽  
Two Component Systems ◽  
Processing Peptidase

This study characterized the two-component regulatory systems encoded by bfrKRT and cemAKR, and assessed their influence on biofilm formation by Lactobacillus reuteri 100-23. A method for deletion of multiple genes was employed to disrupt the genetic loci of two-component systems. The operons bfrKRT and cemAKR showed complementary organization. Genes bfrKRT encode a histidine kinase, a response regulator and an ATP-binding cassette-type transporter with a bacteriocin-processing peptidase domain, respectively. Genes cemAKR code for a signal peptide, a histidine kinase and a response regulator, respectively. Deletion of single or multiple genes in the operons bfrKRT and cemAKR did not affect cell morphology, growth or the sensitivity to various stressors. However, gene disruption affected biofilm formation; this effect was dependent on the carbon source. Deletion of bfrK or cemA increased sucrose-dependent biofilm formation in vitro. Glucose-dependent biofilm formation was particularly increased by deletion of cemK. The expression of cemK and cemR was altered by deletion of bfrK, indicating cross-talk between these two regulatory systems. These results may contribute to our understanding of the genetic factors related to the biofilm formation and competitiveness of L. reuteri in intestinal ecosystems.

scholarly journals Class III Histidine Kinases: a Recently Accessorized Kinase Domain in Putative Modulators of Type IV Pilus-Based Motility

2017 ◽  
Vol 199 (18) ◽  
Author(s):  
Ogun Adebali ◽  
Marharyta G. Petukh ◽  
Alexander O. Reznik ◽  
Artem V. Tishkov ◽  
Amit A. Upadhyay ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Evolutionary History ◽  
Modular Design ◽  
Environmental Changes ◽  
Bacterial Species ◽  
Attractive Potential ◽  
Type Iv Pilus ◽  
Histidine Kinases ◽  
Type Iv ◽  
Signal Transduction Systems

ABSTRACT Histidine kinases are key components of regulatory systems that enable bacteria to respond to environmental changes. Two major classes of histidine kinases are recognized on the basis of their modular design: classical (HKI) and chemotaxis specific (HKII). Recently, a new type of histidine kinase that appeared to have features of both HKIs and HKIIs was identified and termed HKIII; however, the details of HKIII's relationship to other two classes of histidine kinases, their function, and evolutionary history remain unknown. Here, we carried out genomic, phylogenetic, and protein sequence analyses that allowed us to reveal the unusual evolutionary history of this protein family, formalize its distinctive features, and propose its putative function. HKIIIs are characterized by the presence of sensory domains and the lack of a dimerization domain, which is typically present in all histidine kinases. In addition to a single-domain response regulator, HKIII signal transduction systems utilize CheX phosphatase and, in many instances, an unorthodox soluble chemoreceptor that are usual components of chemotaxis signal transduction systems. However, many HKIII genes are found in genomes completely lacking chemotaxis genes, thus decoupling their function from chemotaxis. By contrast, all HKIII-containing genomes also contain pilT, a marker gene for bacterial type IV pilus-based motility, whose regulation is proposed as a putative function for HKIII. These signal transduction systems have a narrow phyletic distribution but are present in many emerging and opportunistic pathogens, thus offering an attractive potential target for future antimicrobial drug design. IMPORTANCE Bacteria adapt to their environment and their hosts by detecting signals and regulating their cellular functions accordingly. Here, we describe a largely unexplored family of signal transduction histidine kinases, called HKIII, that have a unique modular design. While they are currently identified in a relatively short list of bacterial species, this list contains many emerging pathogens. We show that HKIIIs likely control bacterial motility across solid surfaces, which is a key virulence factor in many bacteria, including those causing severe infections. Full understanding of this putative function may help in designing effective drugs against pathogens that will not affect the majority of the beneficial human microbiome.

scholarly journals The Histidine Kinase Domain of UhpB Inhibits UhpA Action at the Escherichia coli uhpT Promoter

2000 ◽  
Vol 182 (22) ◽  
pp. 6279-6286 ◽  
Author(s):  
Jesse S. Wright ◽  
Igor N. Olekhnovich ◽  
Gail Touchie ◽  
Robert J. Kadner
Keyword(s):  
Escherichia Coli ◽  
Histidine Kinase ◽  
Response Regulator ◽  
Kinase Domain ◽  
Dominant Negative ◽  
Dominant Negative Effect ◽  
Signaling Complex ◽  
Regulatory Systems ◽  
Negative Effect ◽  
Polytopic Membrane Protein

ABSTRACT The histidine kinase (HK) component of many two-component regulatory systems exhibits regulated ability to phosphorylate itself and to participate in transfer of phosphate to and from its cognate response regulator. The signaling system that controls expression of the UhpT sugar phosphate transporter in Escherichia coli in response to external glucose 6-phosphate includes the HK protein UhpB and the polytopic membrane protein UhpC, a UhpT homolog which is required for responsiveness to an inducer and activation of UhpB. The existence of a UhpBC signaling complex is suggested by the requirement for UhpC for the activity of certain constitutively active variants of UhpB, the dominance and epistasis relationships of uhpalleles, and the finding that expression of UhpB in excess of UhpC has a strong dominant-negative effect. Expression of a hybrid protein containing the cytoplasmic C-terminal half of UhpB fused to glutathioneS-transferase (GST) also interfered with Uhp signaling. This interference phenotype could not result solely from the phosphatase activity of UhpB, because interference affected both overexpressed UhpA and UhpA variants which are active in the absence of phosphorylation. Variant forms of UhpB which were active in the absence of UhpC carried amino acid substitutions near motifs conserved in HK proteins. The GST fusion protein inhibited the ability of UhpA to bind and activate transcription at the uhpT promoter. Unlike the wild-type situation, a GST fusion variant carrying one of the UhpB-activating substitutions, R324C, displayed autokinase activity and phosphate transfer to UhpA but retained the ability to sequester UhpA when it was altered in the conserved residues important for phosphate transfer. Thus, the default state of UhpB is kinase off, and activation of its phosphate transfer activity requires either the action of UhpC or the occurrence of certain mutations in UhpB. The interference phenotype shown by UhpB in excess of UhpC appears to include the binding and sequestration of UhpA.

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