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

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.

• Publication year

  2021

• Venue

  Genes

• Publication date

  2021-12-23

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.3390/genes13010034PMID 35052374PMCID 8774646
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Staphylococcal trafficking and infection—from ‘nose to gut’ and back

  2021cited by this paper
• Fluorescence Polarization (FP) Assay for Measuring Staphylococcus aureus Membrane Fluidity.

  2021cited by this paper
• The Role of graRS in Regulating Virulence and Antimicrobial Resistance in Methicillin-Resistant Staphylococcus aureus

  2021cited by this paper
• The extracellular loop of the membrane permease VraG interacts with GraS to sense cationic antimicrobial peptides in Staphylococcus aureus

  2021influential reference
• Fatty acids can inhibit Staphylococcus aureus SaeS activity at the membrane independent of alterations in respiration

  2021cited by this paper
• The Sensor Histidine Kinase ArlS Is Necessary for Staphylococcus aureus To Activate ArlR in Response to Nutrient Availability

  2021cited by this paper
• Rearrangement of Thiodepsipeptides by S → N Acyl Shift Delivers Homodetic Autoinducing Peptides.

  2021influential reference
• Non-Native Peptides Capable of Pan-Activating the agr Quorum Sensing System across Multiple Specificity Groups of Staphylococcus epidermidis.

  2021cited by this paper
• Investigating the effect of an identified mutation within a critical site of PAS domain of WalK protein in a vancomycin-intermediate resistant Staphylococcus aureus by computational approaches

  2021cited by this paper
• Membrane Sensor Histidine Kinases: Insights from Structural, Ligand and Inhibitor Studies of Full-Length Proteins and Signalling Domains for Antibiotic Discovery

  2021cited by this paper
• Role of the Staphylococcus aureus Extracellular Loop of GraS in Resistance to Distinct Human Defense Peptides in PMN and Invasive Cardiovascular infections

  2021cited by this paper
• Novel Functions and Signaling Specificity for the GraS Sensor Kinase of Staphylococcus aureus in Response to Acidic pH

  2020cited by this paper
• Identification of Novel Thermosensors in Gram-Positive Pathogens

  2020cited by this paper
• Interface switch mediates signal transmission in a two-component system

  2020influential reference
• The Staphylococcus aureus ArlRS two‐component system regulates virulence factor expression through MgrA

  2020cited by this paper
• Structure-Activity-Relationship Studies of Small Molecule Modulators of the Staphylococcal Accessory Gene Regulator.

  2020cited by this paper
• The impact of two-component sensorial network in staphylococcal speciation

  2020cited by this paper
• Role of respiratory NADH oxidation in the regulation of Staphylococcus aureus virulence

  2020cited by this paper
• The SrrAB two-component system regulates Staphylococcus aureus pathogenicity through redox sensitive cysteines

  2020influential reference
• Environmental conditions dictate differential evolution of vancomycin resistance in Staphylococcus aureus

  2020cited by this paper
• YycH and YycI Regulate Expression of Staphylococcus aureus Autolysins by Activation of WalRK Phosphorylation

  2020cited by this paper
• Detection of heterogeneous vancomycin intermediate resistance in MRSA isolates from Latin America.

  2020cited by this paper
• Discovery of quorum quenchers targeting the membrane-embedded sensor domain of the Staphylococcus aureus receptor histidine kinase, AgrC.

  2020cited by this paper
• Systematic Reconstruction of the Complete Two-Component Sensorial Network in Staphylococcus aureus

  2020cited by this paper
• Timing is everything - impact of naturally occurring Staphylococcus aureus AgrC cytoplasmic domain adaptive mutations on auto-induction.

  2019cited by this paper
• Control of Staphylococcus aureus Quorum Sensing by a Membrane-Embedded Peptidase

  2019cited by this paper
• Disruption of Glycolysis by Nutritional Immunity Activates a Two-Component System That Coordinates a Metabolic and Antihost Response by Staphylococcus aureus

  2019cited by this paper
• Single mutations in BraRS confer high resistance against nisin A in Staphylococcus aureus

  2019cited by this paper
• Identification of Small Molecules Exhibiting Oxacillin Synergy through a Novel Assay for Inhibition of vraTSR Expression in Methicillin-Resistant Staphylococcus aureus

  2019influential reference
• Methicillin-resistant Staphylococcus aureus: an overview of basic and clinical research

  2019cited by this paper
• Control of the bifunctional O2‐sensor kinase NreB of Staphylococcus carnosus by the nitrate sensor NreA: Switching from kinase to phosphatase state

  2019cited by this paper
• Identification of a Molecular Latch that Regulates Staphylococcal Virulence.

  2019cited by this paper
• Transmembrane Prolines Mediate Signal Sensing and Decoding in Bacillus subtilis DesK Histidine Kinase

  2019cited by this paper
• Homeostatic control of cell wall hydrolysis by the WalRK two-component signaling pathway in Bacillus subtilis

  2019cited by this paper
• MroQ Is a Novel Abi-Domain Protein That Influences Virulence Gene Expression in Staphylococcus aureus via Modulation of Agr Activity

  2019influential reference
• The role of ArlRS in regulating oxacillin susceptibility in methicillin-resistant Staphylococcus aureus indicates it is a potential target for antimicrobial resistance breakers

  2019cited by this paper
• Phosphate signaling through alternate conformations of the PstSCAB phosphate transporter

  2018cited by this paper
• Sensory deprivation in Staphylococcus aureus

  2018cited by this paper
• SpdC, a novel virulence factor, controls histidine kinase activity in Staphylococcus aureus

  2018influential reference
• Nutritional Regulation of the Sae Two-Component System by CodY in Staphylococcus aureus

  2018cited by this paper
• The FDA-approved anti-cancer drugs, streptozotocin and floxuridine, reduce the virulence of Staphylococcus aureus

  2018influential reference
• Zinc-binding to the cytoplasmic PAS domain regulates the essential WalK histidine kinase of Staphylococcus aureus

  2018cited by this paper
• Coordinated regulation of transcription by CcpA and the Staphylococcus aureus two-component system HptRS

  2018cited by this paper
• Aspartic Acid Residue 51 of SaeR Is Essential for Staphylococcus aureus Virulence

  2018cited by this paper
• Staphylococcus aureus Uses the GraXRS Regulatory System To Sense and Adapt to the Acidified Phagolysosome in Macrophages

  2018cited by this paper
• PhoPR Contributes to Staphylococcus aureus Growth during Phosphate Starvation and Pathogenesis in an Environment-Specific Manner

  2018cited by this paper
• Activation of the PhoPR-Mediated Response to Phosphate Limitation Is Regulated by Wall Teichoic Acid Metabolism in Bacillus subtilis

  2018cited by this paper
• Comparative Genomics of Staphylococcus Reveals Determinants of Speciation and Diversification of Antimicrobial Defense

  2018cited by this paper
• Glycopeptide resistance: Links with inorganic phosphate metabolism and cell envelope stress.

  2017cited by this paper
• Signal Sensing and Transduction by Histidine Kinases as Unveiled through Studies on a Temperature Sensor.

  2017cited by this paper
• Role of Fatty Acid Kinase in Cellular Lipid Homeostasis and SaeRS-Dependent Virulence Factor Expression in Staphylococcus aureus

  2017cited by this paper
• The cell wall precursor lipid II acts as a molecular signal for the Ser/Thr kinase PknB of Staphylococcus aureus.

  2017influential reference
• Vancomycin susceptibility in methicillin-resistant Staphylococcus aureus is mediated by YycHI activation of the WalRK essential two-component regulatory system

  2016cited by this paper
• Regulation of Virulence in Staphylococcus aureus: Molecular Mechanisms and Remaining Puzzles.

  2016influential reference
• Transcriptional Analysis and Subcellular Protein Localization Reveal Specific Features of the Essential WalKR System in Staphylococcus aureus

  2016cited by this paper
• Characterization of structural elements in native autoinducing peptides and non-native analogues that permit the differential modulation of AgrC-type quorum sensing receptors in Staphylococcus aureus.

  2016cited by this paper
• SpoVG Regulates Cell Wall Metabolism and Oxacillin Resistance in Methicillin-Resistant Staphylococcus aureus Strain N315

  2016cited by this paper
• Impact of Environmental Cues on Staphylococcal Quorum Sensing and Biofilm Development*

  2016cited by this paper
• Structural Studies on the Extracellular Domain of Sensor Histidine Kinase YycG from Staphylococcus aureus and Its Functional Implications.

  2016cited by this paper
• Staphylococcus aureus RNAIII and Its Regulon Link Quorum Sensing, Stress Responses, Metabolic Adaptation, and Regulation of Virulence Gene Expression.

  2016cited by this paper
• VfrB Is a Key Activator of the Staphylococcus aureus SaeRS Two-Component System

  2016cited by this paper
• The SaeRS Two-Component System of Staphylococcus aureus

  2016influential reference
• SrrAB Modulates Staphylococcus aureus Cell Death through Regulation of cidABC Transcription

  2016cited by this paper
• Signaling mechanism by the Staphylococcus aureus two-component system LytSR: role of acetyl phosphate in bypassing the cell membrane electrical potential sensor LytS

  2016cited by this paper
• Regulatory mechanism of the three-component system HptRSA in glucose-6-phosphate uptake in Staphylococcus aureus

  2016cited by this paper
• Bacterial Hypoxic Responses Revealed as Critical Determinants of the Host-Pathogen Outcome by TnSeq Analysis of Staphylococcus aureus Invasive Infection

  2015cited by this paper
• The AirSR two-component system contributes to Staphylococcus aureus survival in human blood and transcriptionally regulates sspABC operon

  2015cited by this paper
• Identification of the amino acids essential for LytSR‐mediated signal transduction in Staphylococcus aureus and their roles in biofilm‐specific gene expression

  2015influential reference
• Signaling mechanism by the Staphylococcus aureus two-component system LytSR: role of acetyl phosphate in bypassing the cell membrane electrical potential sensor LytS.

  2015influential reference
• The Extracytoplasmic Linker Peptide of the Sensor Protein SaeS Tunes the Kinase Activity Required for Staphylococcal Virulence in Response to Host Signals

  2015cited by this paper
• Binding of Cyclic Di-AMP to the Staphylococcus aureus Sensor Kinase KdpD Occurs via the Universal Stress Protein Domain and Downregulates the Expression of the Kdp Potassium Transporter

  2015cited by this paper
• Calprotectin Increases the Activity of the SaeRS Two Component System and Murine Mortality during Staphylococcus aureus Infections

  2015influential reference
• Investigational therapies targeting quorum-sensing for the treatment of Staphylococcus aureus infections

  2015cited by this paper
• Characterization of a Novel Two-Component Regulatory System, HptRS, the Regulator for the Hexose Phosphate Transport System in Staphylococcus aureus

  2015cited by this paper
• Activation and inhibition of the receptor histidine kinase AgrC occurs through opposite helical transduction motions.

  2014cited by this paper
• Diversity of two-component systems: insights into the signal transduction mechanism by the  Staphylococcus aureus two-component system GraSR.

  2014cited by this paper
• Site-Specific Mutation of the Sensor Kinase GraS in Staphylococcus aureus Alters the Adaptive Response to Distinct Cationic Antimicrobial Peptides

  2014cited by this paper
• Differential regulation of staphylococcal virulence by the sensor kinase SaeS in response to neutrophil-derived stimuli

  2014cited by this paper
• Diversity of two-component systems: insights into the signal transduction mechanism by the Staphylococcus aureus two-component system GraSR

  2014cited by this paper
• The PhoU Protein from Escherichia coli Interacts with PhoR, PstB, and Metals To Form a Phosphate-Signaling Complex at the Membrane

  2014cited by this paper
• Altering gene expression by aminocoumarins: the role of DNA supercoiling in Staphylococcus aureus

  2014cited by this paper
• Investigating the genetic regulation of the ECF sigma factor σS in Staphylococcus aureus

  2014cited by this paper
• Modulation of cell wall synthesis and susceptibility to vancomycin by the two-component system AirSR in Staphylococcus aureus NCTC8325

  2013cited by this paper
• Role of the LytSR Two-Component Regulatory System in Adaptation to Cationic Antimicrobial Peptides in Staphylococcus aureus

  2013influential reference
• The Staphylococcus aureus SrrAB Two-Component System Promotes Resistance to Nitrosative Stress and Hypoxia

  2013cited by this paper
• Structural characterization of native autoinducing peptides and abiotic analogues reveals key features essential for activation and inhibition of an AgrC quorum sensing receptor in Staphylococcus aureus.

  2013cited by this paper
• WalK, the Path towards New Antibacterials with Low Potential for Resistance Development.

  2013cited by this paper
• The Ktr potassium transport system in Staphylococcus aureus and its role in cell physiology, antimicrobial resistance and pathogenesis

  2013cited by this paper
• The KdpD/KdpE Two-Component System: Integrating K+ Homeostasis and Virulence

  2013cited by this paper
• Silkworm Apolipophorin Protein Inhibits Hemolysin Gene Expression of Staphylococcus aureus via Binding to Cell Surface Lipoteichoic Acids*

  2013influential reference
• Transcriptional Profiling of Staphylococcus aureus During Growth in 2 M NaCl Leads to Clarification of Physiological Roles for Kdp and Ktr K+ Uptake Systems

  2013cited by this paper
• RNase Y of Staphylococcus aureus and its role in the activation of virulence genes

  2012cited by this paper
• AirSR, a [2Fe-2S] cluster-containing two-component system, mediates global oxygen sensing and redox signaling in Staphylococcus aureus.

  2012cited by this paper
• Staphylococcus aureus determinants for nasal colonization.

  2012cited by this paper
• Purification and Activity Testing of the Full-Length YycFGHI Proteins of Staphylococcus aureus

  2012cited by this paper
• The auxiliary protein complex SaePQ activates the phosphatase activity of sensor kinase SaeS in the SaeRS two‐component system of Staphylococcus aureus

  2012cited by this paper
• The WalKR System Controls Major Staphylococcal Virulence Genes and Is Involved in Triggering the Host Inflammatory Response

  2012cited by this paper
• Investigation of the Staphylococcus aureus GraSR Regulon Reveals Novel Links to Virulence, Stress Response and Cell Wall Signal Transduction Pathways

  2011cited by this paper
• NsaRS is a cell-envelope-stress-sensing two-component system of Staphylococcus aureus.

  2011cited by this paper
• Negative control in two‐component signal transduction by transmitter phosphatase activity

  2011cited by this paper

• Mutation-based mechanisms of antibiotic resistance

  2026cites this paper
• Hijacking the signal: a critical evaluation of quorum sensing inhibitors as a next-generation approach against Staphylococcus aureus

  2026cites this paper
• Quorum sensing in bacteria: insights into communication and inhibition strategies—a review

  2026cites this paper
• Differential Pathogenic and Commensal Response of Staphylococcus aureus and Staphylococcus epidermidis Towards Chemical Signals of Human Skin

  2026cites this paper
• Antimicrobial efficacy of Bifidobacterium longum FB1-4 cell-free supernatant against MRSA: insights into mechanisms and food matrix application

  2026cites this paper
• Extended Shine-Dalgarno motifs govern translation initiation in Staphylococcus aureus.

  2026cites this paper
• The anti-biofilm compound 4-ethoxybenzoic acid inhibits Staphylococcus aureus virulence factor production via a putative 4EB-binding pocket in key virulence-associated proteins

  2026influential citation
• Universal receptive system as a novel regulator of transcriptomic activity of Staphylococcus aureus

  2025cites this paper
• Calprotectin protects Staphylococcus aureus in coculture with Pseudomonas aeruginosa by attenuating quorum sensing and decreasing the production of pseudomonal antimicrobials

  2025cites this paper
• Untangling the Complexity of Two-Component Signal Transduction in Bacteria

  2025cites this paper
• AuxB interacts directly with GpsB and PknB to coordinate cell envelope processes that contribute to intrinsic antibiotic resistance in Staphylococcus aureus

  2025cites this paper
• The Susceptibility Profiles of Human Peripheral Blood Cells to Staphylococcus aureus Cytotoxins

  2025cites this paper
• Bactofencin A Displays a Delayed Killing Effect on a Clinical Strain of Staphylococcus aureus Which Is Greatly Accelerated in the Presence of Nisin

  2025cites this paper
• Global changes in Staphylococcus aureus virulence and metabolism during colonization of healthy skin

  2025cites this paper
• Pyrimidine sufficiency is required for Sae two-component system signaling in Staphylococcus aureus

  2025cites this paper
• Mechanism of antibacterial and antibiofilm of thiazolidinone derivative TD-H2-A against Staphylococcus aureus

  2025cites this paper
• Quorum Sensing: Not Just a Bridge Between Bacteria

  2025cites this paper
• A Staphylococcus aureus Virulence Inhibitor Identified by SaeRS Refactoring and Screening in Bacillus subtilis.

  2025cites this paper
• Global cross-genome comparison of carbohydrate transporters in Staphylococcus aureus with distinct antimicrobial susceptibility profiles

  2025cites this paper
• Genomic-transcriptomic analysis of Staphylococcus aureus biofilm formation under sub-MIC antibiotic exposure.

  2025cites this paper
• Activation of the Staphylococcus aureus intramembrane sensing histidine kinase SaeS via intramembrane interaction with the bacterially encoded small protein ScrA

  2025cites this paper
• Pyrimidine sufficiency is required for Sae two-component system signaling in Staphylococcus aureus

  2025influential citation
• Staphylococcus aureus sensor histidine kinase VraS mutations linked to antibiotic resistance affect enzymatic catalysis, stability, and substrate interactions.

  2025cites this paper
• Impact of Sinus Surgery on Bacteriome Composition in Patients With Chronic Rhinosinusitis With Nasal Polyps

  2025cites this paper
• Punicalagin inhibits Staphylococcus aureus growth and biofilm formation: integrated omics reveals potential mechanisms

  2025cites this paper
• Molecular mechanisms of resistance and tolerance of Staphylococcus aureus to daptomycin.

  2025cites this paper
• Master transcriptional regulator SaeS in Staphylococcus aureus contributes to staphyloxanthin biosynthesis to promote survival during invasive infection

  2025cites this paper
• Hemolysis of Human Erythrocytes by Methicillin-Resistant Staphylococcus aureus Is Primarily Caused by PSMα Peptides

  2025cites this paper
• Beyond commensalism: genomic insights into micrococcin P1-producing Staphylococcus chromogenes

  2025cites this paper
• Multiple clades of regulators contribute to bacterial phosphate homeostasis and pathogenesis

  2025cites this paper
• Immune dysfunction during S. aureus biofilm-associated implant infections: opportunities for novel therapeutic strategies

  2025cites this paper
• The Staphylococcus aureus esterase FmtA is essential for wall teichoic acid D-alanylation

  2025cites this paper
• The two-component system ArlRS is essential for wall teichoic acid glycoswitching in Staphylococcus aureus

  2024cites this paper
• Staphylococcus aureus biofilm: Formulation, regulatory, and emerging natural products-derived therapeutics

  2024cites this paper
• The Staphylococcus aureus CamS lipoprotein is a repressor of toxin production that shapes host-pathogen interaction

  2024cites this paper
• Staphylococcus aureus enters viable-but-nonculturable state in response to chitooligosaccharide stress by altering metabolic pattern and transmembrane transport function.

  2024cites this paper
• Ribosome Profiling Methods Adapted to the Study of RNA-Dependent Translation Regulation in Staphylococcus aureus.

  2024cites this paper
• The role of human extracellular matrix proteins in defining Staphylococcus aureus biofilm infections

  2024cites this paper
• L-arginine supplementation abrogates hypoxia-induced virulence of Staphylococcus aureus in a murine diabetic pressure wound model

  2024cites this paper
• Crosstalk involving two-component systems in Staphylococcus aureus signaling networks

  2024cites this paper
• Regulation of heme biosynthesis via the coproporphyrin dependent pathway in bacteria

  2024cites this paper
• Accessory Gene Regulator (agr) group polymorphisms in methicillin-resistant Staphylococcus aureus and its association with biofilm formation.

  2024cites this paper
• Repeated Exposure of Vancomycin to Vancomycin-Susceptible Staphylococcusaureus (VSSA) Parent Emerged VISA and VRSA Strains with Enhanced Virulence Potentials

  2024cites this paper
• Antibacterial HA-coatings on bioresorbable Mg alloy

  2024cites this paper
• Targeting New Functions and Applications of Bacterial Two‐Component Systems

  2024cites this paper
• Staphylococcus aureus response and adaptation to vancomycin.

  2024cites this paper
• Transcriptional Profiling of Staphylococcus aureus during the Transition from Asymptomatic Nasal Colonization to Skin Colonization/Infection in Patients with Atopic Dermatitis

  2024cites this paper
• Mechanism of activation and autophosphorylation of a histidine kinase

  2024cites this paper
• Functional Study of desKR: a Lineage-Specific Two-Component System Positively Regulating Staphylococcus aureus Biofilm Formation

  2024cites this paper
• The association of dextran sodium sulfate to the bioactive agent I-modulia® attenuates Staphylococcus aureus virulence expression and δ-toxin production.

  2024cites this paper
• Latest research progress on anti-microbial effects, mechanisms of action, and product developments of dietary flavonoids: A systematic literature review

  2024cites this paper
• Universal Receptive System as a novel regulator of transcriptomic activity of Staphylococcus aureus

  2024cites this paper
• Riboflavin as an Anti-Virulence Agent Against Staphylococcus aureus

  2024cites this paper
• Secretory proteins in the orchestration of microbial virulence: The curious case of Staphylococcus aureus.

  2023cites this paper
• Inside the phagosome: A bacterial perspective

  2023cites this paper
• TetR and OmpR family regulators in natural product biosynthesis and resistance

  2023cites this paper
• GraS signaling in Staphylococcus aureus is regulated by a single D35 residue in the extracellular loop

  2023cites this paper
• Genetic alterations in methicillin-susceptible Staphylococcus aureus associated with high vancomycin minimum inhibitory concentration.

  2023cites this paper
• Combined proteomic and transcriptomic analysis of the antimicrobial mechanism of tannic acid against Staphylococcus aureus

  2023cites this paper
• Understanding mechanisms of virulence in MRSA: implications for antivirulence treatment strategies

  2023cites this paper
• Celastrol Combats Methicillin‐Resistant Staphylococcus aureus by Targeting Δ1‐Pyrroline‐5‐Carboxylate Dehydrogenase

  2023cites this paper
• The Small Protein ScrA Influences Staphylococcus aureus Virulence-Related Processes via the SaeRS System

  2023cites this paper
• Enzyme-Responsive Microneedle Patch for Bacterial Infection and Accelerated Healing of Diabetic Wounds

  2023cites this paper
• Regulation of Bacterial Two-Component Systems by Cardiolipin

  2023cites this paper
• Anti-Quorum Sensing Activity of Probiotics: The Mechanism and Role in Food and Gut Health

  2023cites this paper
• The cascade regulation of small RNA and quorum sensing system: Focusing on biofilm formation of foodborne pathogens in food industry

  2023cites this paper
• Effects of flavonoids on membrane adaptation of food-associated bacteria.

  2023cites this paper
• Regulation of Bacterial Two-Component Systems by Cardiolipin

  2023cites this paper
• Targeting the Holy Triangle of Quorum Sensing, Biofilm Formation, and Antibiotic Resistance in Pathogenic Bacteria

  2022cites this paper
• Effect of spdC gene expression on virulence and antibiotic resistance in clinical Staphylococcus aureus isolates

  2022cites this paper
• The influenza-injured lung microenvironment promotes MRSA virulence, contributing to severe secondary bacterial pneumonia.

  2022cites this paper
• Transcriptional adaptation of staphylococci during colonization of the authentic human environment: An overview of transcriptomic changes and their relationship to physiological conditions

  2022cites this paper
• CodY is modulated by YycF and affects biofilm formation in Staphylococcus aureus

  2022cites this paper
• Thirty Years of sRNA-Mediated Regulation in Staphylococcus aureus: From Initial Discoveries to In Vivo Biological Implications

  2022cites this paper
• In silico identification of auxiliary genes required for β-lactam resistance

  year unknowncites this paper