scholarly journals Two-Component Systems of S. aureus: Signaling and Sensing Mechanisms

Genes ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 34
Author(s):  
Lisa Bleul ◽  
Patrice Francois ◽  
Christiane Wolz
Keyword(s):  
Transcriptional Activation ◽  
Drug Targets ◽  
Bacterial Survival ◽  
Histidine Kinases ◽  
Signal Perception ◽  
Signaling Mechanisms ◽  
Component Systems ◽  
Two Component ◽  
Two Component Systems ◽  
Sense And Respond

Staphylococcus aureus encodes 16 two-component systems (TCSs) that enable the bacteria to sense and respond to changing environmental conditions. Considering the function of these TCSs in bacterial survival and their potential role as drug targets, it is important to understand the exact mechanisms underlying signal perception. The differences between the sensing of appropriate signals and the transcriptional activation of the TCS system are often not well described, and the signaling mechanisms are only partially understood. Here, we review present insights into which signals are sensed by histidine kinases in S. aureus to promote appropriate gene expression in response to diverse environmental challenges.

scholarly journals Blue Light Regulated Two-Component Systems: Enzymatic and Functional Analyses of Light-Oxygen-Voltage (LOV)-Histidine Kinases and Downstream Response Regulators

Biochemistry ◽  
2013 ◽  
Vol 52 (27) ◽  
pp. 4656-4666 ◽  
Author(s):  
Fernando Correa ◽  
Wen-Huang Ko ◽  
Victor Ocasio ◽  
Roberto A. Bogomolni ◽  
Kevin H. Gardner
Keyword(s):  
Blue Light ◽  
Response Regulators ◽  
Histidine Kinases ◽  
Component Systems ◽  
Two Component ◽  
Two Component Systems ◽  
Functional Analyses

scholarly journals Cross-regulation between RpfG and HtsHs to regulate antibiotic biosynthesis in Lysobacter

2020 ◽  
Author(s):  
Kaihuai Li ◽  
Gaoge Xu ◽  
Bo Wang ◽  
Guichun Wu ◽  
Fengquan Liu
Keyword(s):  
Gene Expression ◽  
Environmental Changes ◽  
Antibiotic Biosynthesis ◽  
Two Component System ◽  
Independent Manner ◽  
Heat Stable ◽  
Component Systems ◽  
Two Component ◽  
Two Component Systems ◽  
Sense And Respond

AbstractBacterial two-component systems (TCSs) sense and respond to environmental changes and modulate downstream gene expression. However, the mechanism of cross-talk between multiple TCSs is unclear. In this study, we report a previously uncharacterized mechanism by which the TCS protein RpfG interacts with hybrid two-component system (HyTCS) proteins HtsH1, HtsH2 and HtsH3 to regulate antibiotic biosynthesis in Lysobacter. RpfG, a phosphodiesterase (PDE), can degrade c-di-GMP to 5’-pGpG and can regulate antibiotic heat-stable antifungal factor (HSAF) biosynthesis in a PDE- independent manner. Thus, we wondered whether RpfG regulate HSAF biosynthesis through interactions with other factors. Subsequently, we demonstrated that RpfG interacts with three HyTCS proteins (HtsH1, HtsH2 and HtsH3), that can inhibit the PDE enzymatic activity of RpfG. Importantly, deletion of htsH1, htsH2 and htsH3 resulted in significantly decreased HSAF production, and we showed that HtsH1, HtsH2 and HtsH3 depend on their phosphorylation activity to directly regulate HSAF biosynthesis gene expression. Our results reveal that RpfG does not depend on PDE activity to regulate HSAF biosynthesis, rather it interacts with HtsH1, HtsH2 and HtsH3 to do so, a regulatory mechanism that may be a conserved paradigm in Lysobacter and Xanthomonas.

scholarly journals Phosphatase activity of the histidine kinases ensures pathway specificity of the ChrSA and HrrSA two‐component systems in C orynebacterium glutamicum

2014 ◽  
Vol 92 (6) ◽  
pp. 1326-1342 ◽  
Author(s):  
Eva Hentschel ◽  
Christina Mack ◽  
Cornelia Gätgens ◽  
Michael Bott ◽  
Melanie Brocker ◽  
...  
Keyword(s):  
Phosphatase Activity ◽  
Histidine Kinases ◽  
Component Systems ◽  
Two Component ◽  
Two Component Systems

scholarly journals Accurate prediction of bacterial two-component signaling with a deep recurrent neural network ORAKLE

2019 ◽  
Author(s):  
Jan Balewski ◽  
Zachary F. Hallberg
Keyword(s):  
Neural Network ◽  
Amino Acid ◽  
Response Regulator ◽  
Amino Acid Sequences ◽  
Histidine Kinases ◽  
Deep Recurrent Neural Network ◽  
Component Systems ◽  
Two Component ◽  
Two Component Systems ◽  
Recommender Algorithm

AbstractTwo-component systems (2CS) are a primary method that bacteria use to detect and respond to environmental stimuli. Receptor histidine kinases (HK) detect an environmental signal, activating the appropriate response regulator (RR). Genes for such cognate HK-RR pairs are often located proximally on the chromosome, allowing easier identification of the target for a particular signal. However, almost half of all HK and RR proteins are orphans, with no nearby partner, complicating identification of the proteins that respond to a particular signal. To address this problem, we trained a neural network on the amino acid sequences of known 2CS pairs. Next, we developed a recommender algorithm that ranks a set of HKs for an arbitrary fixed RR and arbitrary species whose amino acid sequences are known. The recommender strongly favors known 2CS pairs, and correctly selects orphan pairs in Escherichia coli. We expect that use of these results will permit rapid discovery of orphan HK-RR pairs.

scholarly journals Regulation of signaling directionality revealed by 3D snapshots of a kinase:regulator complex in action

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Felipe Trajtenberg ◽  
Juan A Imelio ◽  
Matías R Machado ◽  
Nicole Larrieux ◽  
Marcelo A Marti ◽  
...  
Keyword(s):  
Bacillus Subtilis ◽  
Response Regulators ◽  
Histidine Kinases ◽  
Signaling Systems ◽  
Input Signals ◽  
Component Systems ◽  
Two Component ◽  
Two Component Systems ◽  
Conformational Rearrangements ◽  
Phosphoryl Groups

Two-component systems (TCS) are protein machineries that enable cells to respond to input signals. Histidine kinases (HK) are the sensory component, transferring information toward downstream response regulators (RR). HKs transfer phosphoryl groups to their specific RRs, but also dephosphorylate them, overall ensuring proper signaling. The mechanisms by which HKs discriminate between such disparate directions, are yet unknown. We now disclose crystal structures of the HK:RR complex DesK:DesR from Bacillus subtilis, comprising snapshots of the phosphotransfer and the dephosphorylation reactions. The HK dictates the reactional outcome through conformational rearrangements that include the reactive histidine. The phosphotransfer center is asymmetric, poised for dissociative nucleophilic substitution. The structural bases of HK phosphatase/phosphotransferase control are uncovered, and the unexpected discovery of a dissociative reactional center, sheds light on the evolution of TCS phosphotransfer reversibility. Our findings should be applicable to a broad range of signaling systems and instrumental in synthetic TCS rewiring.

scholarly journals Pangenome analytics reveal two-component systems as conserved targets in ESKAPEE pathogens

2020 ◽  
Author(s):  
Akanksha Rajput ◽  
Yara Seif ◽  
Kumari Sonal Choudhary ◽  
Christopher Dalldorf ◽  
Saugat Poudel ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Sequence Variation ◽  
Response Regulator ◽  
Cellular Functions ◽  
Gene Orientation ◽  
Component Systems ◽  
Two Component ◽  
Two Component Systems ◽  
Sense And Respond ◽  
High Degree

AbstractBacteria sense and respond to environmental stimuli through two-component systems (TCSs), that are composed of histidine kinase sensing and response regulator elements. TCSs are ubiquitous and participate in numerous cellular functions. TCSs across the ESKAPEE pathogens, representing the leading causes of nosocomial infections, were characterized using pangenome analytics, including annotation, mapping, pangenomic status, gene orientation, sequence variation, and structure. Our findings fall into two categories. 1) phylogenetic distribution of TCSs: (i) the number and types of TCSs varies between species of the ESKAPEE pathogens; (ii) TCSs are group-specific, i.e., Gram-positive and Gram-negative, except for KdpDE; (iii) most TCSs are conserved among genomes of an ESKAPEE, except in Pseudomonas aeruginosa. 2) sequence variation: (i) at the operon level, the genomic architecture of a TCS operon stratifies into a few discrete classes; and (ii) at the gene sequence level, histidine kinases, responsible for signal sensing, show sequence and structural variability as compared to response regulators that show a high degree of conservation. Taken together, this first comprehensive pangenomic assessment of TCSs reveals a range of strategies deployed by the ESKAPEE pathogens to manifest pathogenicity and antibiotic resistance. It further suggests that the conserved features of TCSs makes them an attractive group of potential targets with which to address antibiotic resistance.

scholarly journals What do archaeal and eukaryotic histidine kinases sense?

F1000Research ◽  
2019 ◽  
Vol 8 ◽  
pp. 2145 ◽  
Author(s):  
Nicolas Papon ◽  
Ann M. Stock
Keyword(s):  
Response Regulator ◽  
Single Step ◽  
Adaptive Responses ◽  
Histidine Kinases ◽  
Regulatory Processes ◽  
Component Systems ◽  
Two Component ◽  
Broad Array ◽  
Domains Of Life ◽  
Two Component Systems

Signal transduction systems configured around a core phosphotransfer step between a histidine kinase and a cognate response regulator protein occur in organisms from all domains of life. These systems, termed two-component systems, constitute the majority of multi-component signaling pathways in Bacteria but are less prevalent in Archaea and Eukarya. The core signaling domains are modular, allowing versatility in configuration of components into single-step phosphotransfer and multi-step phosphorelay pathways, the former being predominant in bacteria and the latter in eukaryotes. Two-component systems regulate key cellular regulatory processes that provide adaptive responses to environmental stimuli and are of interest for the development of antimicrobial therapeutics, biotechnology applications, and biosensor engineering. In bacteria, two-component systems have been found to mediate responses to an extremely broad array of extracellular and intracellular chemical and physical stimuli, whereas in archaea and eukaryotes, the use of two-component systems is more limited. This review summarizes recent advances in exploring the repertoire of sensor histidine kinases in the Archaea and Eukarya domains of life.

scholarly journals Specificity Residues Determine Binding Affinity for Two-Component Signal Transduction Systems

mBio ◽  
2013 ◽  
Vol 4 (6) ◽  
Author(s):  
Jonathan W. Willett ◽  
Nitija Tiwari ◽  
Susanne Müller ◽  
Katherine R. Hummels ◽  
Jon C. D. Houtman ◽  
...  
Keyword(s):  
Binding Affinity ◽  
Myxococcus Xanthus ◽  
Titration Calorimetry ◽  
Signaling Proteins ◽  
Response Regulators ◽  
Histidine Kinases ◽  
Content Type ◽  
Component Systems ◽  
Two Component ◽  
Two Component Systems

ABSTRACTTwo-component systems (TCS) comprise histidine kinases and their cognate response regulators and allow bacteria to sense and respond to a wide variety of signals. Histidine kinases (HKs) phosphorylate and dephosphorylate their cognate response regulators (RRs) in response to stimuli. In general, these reactions appear to be highly specific and require an appropriate association between the HK and RR proteins. TheMyxococcus xanthusgenome encodes one of the largest repertoires of signaling proteins in bacteria (685 open reading frames [ORFs]), including at least 127 HKs and at least 143 RRs. Of these, 27 arebona fideNtrC-family response regulators, 21 of which are encoded adjacent to their predicted cognate kinases. Using system-wide profiling methods, we determined that the HK-NtrC RR pairs display a kinetic preference during both phosphotransfer and phosphatase functions, thereby defining cognate signaling systems inM. xanthus. Isothermal titration calorimetry measurements indicated that cognate HK-RR pairs interact with dissociation constants (Kd) of approximately 1 µM, while noncognate pairs had no measurable binding. Lastly, a chimera generated between the histidine kinase, CrdS, and HK1190 revealed that residues conferring phosphotransfer and phosphatase specificity dictate binding affinity, thereby establishing discrete protein-protein interactions which prevent cross talk. The data indicate that binding affinity is a critical parameter governing system-wide signaling fidelity for bacterial signal transduction proteins.IMPORTANCEUsingin vitrophosphotransfer and phosphatase profiling assays and isothermal titration calorimetry, we have taken a system-wide approach to demonstrate specificity for a family of two-component signaling proteins inMyxococcus xanthus. Our results demonstrate that previously identified specificity residues dictate binding affinity and that phosphatase specificity follows phosphotransfer specificity for cognate HK-RR pairs. The data indicate that preferential binding affinity is the basis for signaling fidelity in bacterial two-component systems.

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