scholarly journals The response regulator PhoP4 is required for late developmental events in Myxococcus xanthus

Microbiology ◽  
2006 ◽  
Vol 152 (6) ◽  
pp. 1609-1620 ◽  
Author(s):  
Vinh D. Pham ◽  
Conrad W. Shebelut ◽  
Ivy R. Jose ◽  
David A. Hodgson ◽  
David E. Whitworth ◽  
...  
Keyword(s):  
Histidine Kinase ◽  
Response Regulator ◽  
Myxococcus Xanthus ◽  
Kinase Gene ◽  
Spore Viability ◽  
Phenotypic Differences ◽  
Component Systems ◽  
Two Component Systems ◽  
Identification And Characterization

Phosphate regulation is complex in the developmental prokaryote Myxococcus xanthus, and requires at least four two-component systems (TCSs). Here, the identification and characterization of a member of one TCS, designated PhoP4, is reported. phoP4 insertion and in-frame deletion strains caused spore viability to be decreased by nearly two orders of magnitude, and reduced all three development-specific phosphatase activities by 80–90 % under phosphate-limiting conditions. Microarray and quantitative PCR analyses demonstrated that PhoP4 is also required for appropriate expression of the predicted pstSCAB–phoU operon of inorganic phosphate assimilation genes. Unlike the case for the other three M. xanthus Pho TCSs, the chromosomal region around phoP4 does not contain a partner histidine kinase gene. Yeast two-hybrid analyses reveal that PhoP4 interacts reciprocally with PhoR2, the histidine kinase of the Pho2 TCS; however, the existence of certain phenotypic differences between phoP4 and phoR2 mutants suggests that PhoP4 interacts with another, as-yet unidentified, histidine kinase.

scholarly journals Molecular Characterization of Two-Component Systems of Helicobacter pylori

2000 ◽  
Vol 182 (8) ◽  
pp. 2068-2076 ◽  
Author(s):  
Dagmar Beier ◽  
Rainer Frank
Keyword(s):  
Helicobacter Pylori ◽  
Histidine Kinase ◽  
Response Regulator ◽  
Response Regulators ◽  
Reading Frame ◽  
Component Systems ◽  
Two Component ◽  
Two Component Systems

ABSTRACT Two-component systems are frequently involved in the adaptation of bacteria to changing environmental conditions at the level of transcriptional regulation. Here we report the characterization of members of the two-component systems of the gastric pathogenHelicobacter pylori deduced from the genome sequence of strain 26695. We demonstrate that the response regulators HP166, HP1043, and HP1021 have essential functions, as disruption of the corresponding genes is lethal for the bacteria, irrespective of the fact that HP1043 and HP1021 have nonconserved substitutions in crucial amino acids of their receiver domains. An analysis of the in vitro phosphorylation properties of the two-component proteins demonstrates that HP244-HP703 and HP165-HP166 are cognate histidine kinase-response regulator pairs. Furthermore, we provide evidence that the variability of the histidine kinase HP165 caused by a poly(C) tract of variable length close to the 3′ end of open reading frame 165/164 does not interfere with the kinase activity of the transmitter domain of HP165.

scholarly journals Effect of new alleles of the histidine kinase gene ciaH on the activity of the response regulator CiaR in Streptococcus pneumoniae R6

Microbiology ◽  
2011 ◽  
Vol 157 (11) ◽  
pp. 3104-3112 ◽  
Author(s):  
Miriam Müller ◽  
Patrick Marx ◽  
Regine Hakenbeck ◽  
Reinhold Brückner
Keyword(s):  
Streptococcus Pneumoniae ◽  
Histidine Kinase ◽  
Response Regulator ◽  
Regulatory System ◽  
Competence Development ◽  
Kinase Gene ◽  
Lactam Antibiotic ◽  
Spontaneous Mutants ◽  
New Alleles

The two-component regulatory system CiaRH of Streptococcus pneumoniae affects β-lactam susceptibility, autolysis, bacteriocin production, competence development, host colonization and virulence. The system was discovered in a screen for S. pneumoniae R6 mutants resistant to the β-lactam antibiotic cefotaxime. A mutation in the histidine kinase gene ciaH led to this phenotype by enhancing CiaR-mediated gene expression. Additional mutations in ciaH have been described in other spontaneous β-lactam-resistant mutants of S. pneumoniae R6, but their influence on CiaR-mediated gene regulation has not been determined. Likewise, altered ciaH alleles are present in clinical S. pneumoniae isolates, none of which had been characterized. These novel ciaH variants were introduced into S. pneumoniae R6 to measure their ability to activate CiaR-dependent regulation. The ciaH alleles from spontaneous mutants obtained in the laboratory increased the activity of CiaR-dependent promoters between four- and 26-fold, while variants from clinical strains were less effective, with a threefold activation at most. Accordingly, phenotypes associated with a hyperactive CiaRH system, β-lactam resistance, and prevention of competence development, were far more pronounced in the laboratory mutants. Amino acid changes affecting CiaH function were positioned throughout the protein. Five of the most activating changes are located close to the conserved histidine and one in the extracytoplasmic sensor domain. The characterization of new alleles of ciaH expands the spectrum of CiaH variants, which may help to elucidate signal transduction of this important regulatory system. Our study also demonstrates that ciaH alleles overstimulating CiaR regulon expression are present in clinical isolates of S. pneumoniae.

scholarly journals Molecular basis of unidirectional information transmission in two-component systems: lessons from the DesK-DesR thermosensor

2021 ◽  
Author(s):  
Sofia Lima ◽  
Juan Blanco ◽  
Federico Olivieri ◽  
Juan Andres Imelio ◽  
Federico Carrion ◽  
...  
Keyword(s):  
Histidine Kinase ◽  
Regulatory Networks ◽  
Response Regulator ◽  
Signal Transmission ◽  
Phosphoryl Transfer ◽  
Signaling Systems ◽  
Component Systems ◽  
Two Component ◽  
Two Component Systems ◽  
Histidine Phosphorylation

Cellular signaling systems transmit information over long distances using allosteric transitions and/or post-translational modifications. In two-component systems the sensor histidine kinase and response regulator are wired through phosphoryl-transfer reactions, using either a uni- or bi-directional transmission mode, allowing to build rich regulatory networks. Using the thermosensor DesK-DesR two-component system from Bacillus subtilis and combining crystal structures, QM/MM calculations and integrative kinetic modeling, we uncover that: i) longer or shorter distances between the phosphoryl-acceptor and -donor residues can shift the phosphoryl-transfer equilibrium; ii) the phosphorylation-dependent dimerization of the regulator acts as a sequestering mechanism by preventing the interaction with the histidine kinase; and iii) the kinase's intrinsic conformational equilibrium makes the phosphotransferase state unlikely in the absence of histidine phosphorylation, minimizing backwards transmission. These mechanisms allow the system to control the direction of signal transmission in a very efficient way, showcasing the key role that structure-encoded allostery plays in signaling proteins to store and transmit information.

scholarly journals Regulation of Virulence by Two-Component Systems in Pathogenic Burkholderia

2020 ◽  
Vol 88 (7) ◽  
Author(s):  
Matthew M. Schaefers
Keyword(s):  
Histidine Kinase ◽  
Burkholderia Cepacia ◽  
Target Genes ◽  
Response Regulator ◽  
Pharmaceutical Products ◽  
Phosphoryl Group ◽  
Content Type ◽  
Component Systems ◽  
Two Component ◽  
Two Component Systems

ABSTRACT The regulation and timely expression of bacterial genes during infection is critical for a pathogen to cause an infection. Bacteria have multiple mechanisms to regulate gene expression in response to their environment, one of which is two-component systems (TCS). TCS have two components. One component is a sensory histidine kinase (HK) that autophosphorylates when activated by a signal. The activated sensory histidine kinase then transfers the phosphoryl group to the second component, the response regulator, which activates transcription of target genes. The genus Burkholderia contains members that cause human disease and are often extensively resistant to many antibiotics. The Burkholderia cepacia complex (BCC) can cause severe lung infections in patients with cystic fibrosis (CF) or chronic granulomatous disease (CGD). BCC members have also recently been associated with several outbreaks of bacteremia from contaminated pharmaceutical products. Separate from the BCC is Burkholderia pseudomallei, which is the causative agent of melioidosis, a serious disease that occurs in the tropics, and a potential bioterrorism weapon. Bioinformatic analysis of sequenced Burkholderia isolates predicts that most strains have at least 40 TCS. The vast majority of these TCS are uncharacterized both in terms of the signals that activate them and the genes that are regulated by them. This review will highlight TCS that have been described to play a role in virulence in either the BCC or B. pseudomallei. Since many of these TCS are involved in virulence, TCS are potential novel therapeutic targets, and elucidating their function is critical for understanding Burkholderia pathogenesis.

scholarly journals Allosteric Activation of Bacterial Response Regulators: the Role of the Cognate Histidine Kinase Beyond Phosphorylation

mBio ◽  
2014 ◽  
Vol 5 (6) ◽  
Author(s):  
Felipe Trajtenberg ◽  
Daniela Albanesi ◽  
Natalia Ruétalo ◽  
Horacio Botti ◽  
Ariel E. Mechaly ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Histidine Kinase ◽  
Response Regulator ◽  
Activation Mechanism ◽  
Response Regulators ◽  
Content Type ◽  
Component Systems ◽  
Two Component ◽  
Two Component Systems

ABSTRACT Response regulators are proteins that undergo transient phosphorylation, connecting specific signals to adaptive responses. Remarkably, the molecular mechanism of response regulator activation remains elusive, largely because of the scarcity of structural data on multidomain response regulators and histidine kinase/response regulator complexes. We now address this question by using a combination of crystallographic data and functional analyses in vitro and in vivo, studying DesR and its cognate sensor kinase DesK, a two-component system that controls membrane fluidity in Bacillus subtilis. We establish that phosphorylation of the receiver domain of DesR is allosterically coupled to two distinct exposed surfaces of the protein, controlling noncanonical dimerization/tetramerization, cooperative activation, and DesK binding. One of these surfaces is critical for both homodimerization- and kinase-triggered allosteric activations. Moreover, DesK induces a phosphorylation-independent activation of DesR in vivo, uncovering a novel and stringent level of specificity among kinases and regulators. Our results support a model that helps to explain how response regulators restrict phosphorylation by small-molecule phosphoryl donors, as well as cross talk with noncognate sensors. IMPORTANCE The ability to sense and respond to environmental variations is an essential property for cell survival. Two-component systems mediate key signaling pathways that allow bacteria to integrate extra- or intracellular signals. Here we focus on the DesK/DesR system, which acts as a molecular thermometer in B. subtilis, regulating the cell membrane’s fluidity. Using a combination of complementary approaches, including determination of the crystal structures of active and inactive forms of the response regulator DesR, we unveil novel molecular mechanisms of DesR’s activation switch. In particular, we show that the association of the cognate histidine kinase DesK triggers DesR activation beyond the transfer of the phosphoryl group. On the basis of sequence and structural analyses of other two-component systems, this activation mechanism appears to be used in a wide range of sensory systems, contributing a further level of specificity control among different signaling pathways.

scholarly journals Phenotype MicroArray Analysis of Escherichia coli K-12 Mutants with Deletions of All Two-Component Systems

2003 ◽  
Vol 185 (16) ◽  
pp. 4956-4972 ◽  
Author(s):  
Lu Zhou ◽  
Xiang-He Lei ◽  
Barry R. Bochner ◽  
Barry L. Wanner
Keyword(s):  
Escherichia Coli ◽  
Histidine Kinase ◽  
Response Regulator ◽  
Standard Technique ◽  
Common Mechanism ◽  
Phenotype Microarray ◽  
Component Systems ◽  
Two Component ◽  
Two Component Systems ◽  
K 12

ABSTRACT Two-component systems are the most common mechanism of transmembrane signal transduction in bacteria. A typical system consists of a histidine kinase and a partner response regulator. The histidine kinase senses an environmental signal, which it transmits to its partner response regulator via a series of autophosphorylation, phosphotransfer, and dephosphorylation reactions. Much work has been done on particular systems, including several systems with regulatory roles in cellular physiology, communication, development, and, in the case of bacterial pathogens, the expression of genes important for virulence. We used two methods to investigate two-component regulatory systems in Escherichia coli K-12. First, we systematically constructed mutants with deletions of all two-component systems by using a now-standard technique of gene disruption (K. A. Datsenko and B. L. Wanner, Proc. Natl. Acad. Sci. USA 97:6640-6645, 2000). We then analyzed these deletion mutants with a new technology called Phenotype MicroArrays, which permits assays of nearly 2,000 growth phenotypes simultaneously. In this study we tested 100 mutants, including mutants with individual deletions of all two-component systems and several related genes, including creBC-regulated genes (cbrA and cbrBC), phoBR-regulated genes (phoA, phoH, phnCDEFGHIJKLMNOP, psiE, and ugpBAECQ), csgD, luxS, and rpoS. The results of this battery of nearly 200,000 tests provided a wealth of new information concerning many of these systems. Of 37 different two-component mutants, 22 showed altered phenotypes. Many phenotypes were expected, and several new phenotypes were also revealed. The results are discussed in terms of the biological roles and other information concerning these systems, including DNA microarray data for a large number of the same mutants. Other mutational effects are also discussed.

scholarly journals Evolutionary rewiring: a modified prokaryotic gene-regulatory pathway in chloroplasts

2013 ◽  
Vol 368 (1622) ◽  
pp. 20120260 ◽  
Author(s):  
Sujith Puthiyaveetil ◽  
Iskander M. Ibrahim ◽  
John F. Allen
Keyword(s):  
Green Algae ◽  
Gene Transcription ◽  
Response Regulator ◽  
Regulatory System ◽  
Photosynthetic Electron Transport ◽  
Sensor Kinase ◽  
Ps I ◽  
Component Systems ◽  
Two Component Systems ◽  
Gene Regulatory

Photosynthetic electron transport regulates chloroplast gene transcription through the action of a bacterial-type sensor kinase known as chloroplast sensor kinase (CSK). CSK represses photosystem I (PS I) gene transcription in PS I light and thus initiates photosystem stoichiometry adjustment. In cyanobacteria and in non-green algae, CSK homologues co-exist with their response regulator partners in canonical bacterial two-component systems. In green algae and plants, however, no response regulator partner of CSK is found. Yeast two-hybrid analysis has revealed interaction of CSK with sigma factor 1 (SIG1) of chloroplast RNA polymerase. Here we present further evidence for the interaction between CSK and SIG1. We also show that CSK interacts with quinone. Arabidopsis SIG1 becomes phosphorylated in PS I light, which then specifically represses transcription of PS I genes. In view of the identical signalling properties of CSK and SIG1 and of their interactions, we suggest that CSK is a SIG1 kinase. We propose that the selective repression of PS I genes arises from the operation of a gene-regulatory phosphoswitch in SIG1. The CSK-SIG1 system represents a novel, rewired chloroplast-signalling pathway created by evolutionary tinkering. This regulatory system supports a proposal for the selection pressure behind the evolutionary stasis of chloroplast genes.

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