scholarly journals RegA, the Regulator of the Two-Component System RegB/RegA of Brucella suis, Is a Controller of Both Oxidative Respiration and Denitrification Required for Chronic Infection in Mice

2013 ◽  
Vol 81 (6) ◽  
pp. 2053-2061 ◽  
Author(s):  
Elias Abdou ◽  
Amélie Deredjian ◽  
María Pilar Jiménez de Bagüés ◽  
Stephan Köhler ◽  
Véronique Jubier-Maurin
Keyword(s):  
Oxygen Deficiency ◽  
Transcriptional Regulator ◽  
Two Component System ◽  
Component System ◽  
Content Type ◽  
Ubiquinol Oxidase ◽  
Two Component ◽  
Brucella Suis ◽  
Oxidative Respiration

ABSTRACTAdaptation to oxygen deficiency is essential for virulence and persistence ofBrucellainside the host. The flexibility of this bacterium with respect to oxygen depletion is remarkable, sinceBrucella suiscan use an oxygen-dependent transcriptional regulator of the FnrN family, two high-oxygen-affinity terminal oxidases, and a complete denitrification pathway to resist various conditions of oxygen deficiency. Moreover, our previous results suggested that oxidative respiration and denitrification can be simultaneously used byB. suisunder microaerobiosis. The requirement of a functional cytochromebdubiquinol oxidase for nitrite reductase expression evidenced the linkage of these two pathways, and the central role of the two-component system RegB/RegA in the coordinated control of both respiratory systems was demonstrated. We propose a scheme for global regulation ofB. suisrespiratory pathways by the transcriptional regulator RegA, which postulates a role for the cytochromebdubiquinol oxidase in redox signal transmission to the histidine sensor kinase RegB. More importantly, RegA was found to be essential forB. suispersistencein vivowithin oxygen-limited target organs. It is conceivable that RegA acts as a controller of numerous systems involved in the establishment of the persistent state, characteristic of chronic infections byBrucella.

How the PhoP/PhoQ System Controls Virulence and Mg 2+ Homeostasis: Lessons in Signal Transduction, Pathogenesis, Physiology, and Evolution

2021 ◽  
Author(s):  
Eduardo A. Groisman ◽  
Alexandre Duprey ◽  
Jeongjoon Choi
Keyword(s):  
Antimicrobial Agents ◽  
Bacterial Species ◽  
Transcriptional Regulator ◽  
Acidic Ph ◽  
Two Component System ◽  
Component System ◽  
Gram Negative ◽  
Content Type ◽  
Two Component ◽  
Serovar Typhimurium

The PhoP/PhoQ two-component system governs virulence, Mg 2+ homeostasis, and resistance to a variety of antimicrobial agents, including acidic pH and cationic antimicrobial peptides, in several Gram-negative bacterial species. Best understood in Salmonella enterica serovar Typhimurium, the PhoP/PhoQ system consists of the sensor PhoQ and the transcriptional regulator PhoP.

scholarly journals Staphylococcus aureus Nuclease Is an SaeRS-Dependent Virulence Factor

2013 ◽  
Vol 81 (4) ◽  
pp. 1316-1324 ◽  
Author(s):  
Michael E. Olson ◽  
Tyler K. Nygaard ◽  
Laynez Ackermann ◽  
Robert L. Watkins ◽  
Oliwia W. Zurek ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Virulence Factor ◽  
Dependent Manner ◽  
Binding Studies ◽  
Two Component System ◽  
Component System ◽  
Content Type ◽  
Activity Measurements ◽  
Two Component

ABSTRACTSeveral prominent bacterial pathogens secrete nuclease (Nuc) enzymes that have an important role in combating the host immune response. Early studies ofStaphylococcus aureusNuc attributed its regulation to theagrquorum-sensing system. However, recent microarray data have indicated thatnucis under the control of the SaeRS two-component system, which is a major regulator ofS. aureusvirulence determinants. Here we report that thenucgene is directly controlled by the SaeRS two-component system through reporter fusion, immunoblotting, Nuc activity measurements, promoter mapping, and binding studies, and additionally, we were unable identify a notable regulatory link to theagrsystem. The observed SaeRS-dependent regulation was conserved across a wide spectrum of representativeS. aureusisolates. Moreover, with community-associated methicillin-resistantS. aureus(CA MRSA) in a mouse model of peritonitis, we observedin vivoexpression of Nuc activity in an SaeRS-dependent manner and determined that Nuc is a virulence factor that is important forin vivosurvival, confirming the enzyme's role as a contributor to invasive disease. Finally, natural polymorphisms were identified in the SaeRS proteins, one of which was linked to Nuc regulation in a CA MRSA USA300 endocarditis isolate. Altogether, our findings demonstrate that Nuc is an importantS. aureusvirulence factor and part of the SaeRS regulon.

scholarly journals The SaeRS Two-Component System Is a Direct and Dominant Transcriptional Activator of Toxic Shock Syndrome Toxin 1 in Staphylococcus aureus

2016 ◽  
Vol 198 (19) ◽  
pp. 2732-2742 ◽  
Author(s):  
Miren L. Baroja ◽  
Christine A. Herfst ◽  
Katherine J. Kasper ◽  
Stacey X. Xu ◽  
Daniel A. Gillett ◽  
...  
Keyword(s):  
Toxic Shock Syndrome ◽  
Regulatory System ◽  
Transcriptional Regulator ◽  
Transcriptional Activator ◽  
Toxic Shock ◽  
Two Component System ◽  
Component System ◽  
Content Type ◽  
Two Component ◽  
Toxic Shock Syndrome Toxin

ABSTRACTToxic shock syndrome toxin 1 (TSST-1) is aStaphylococcus aureussuperantigen that has been implicated in both menstrual and nonmenstrual toxic shock syndrome (TSS). Despite the important role of TSST-1 in severe human disease, a comprehensive understanding of staphylococcal regulatory factors that control TSST-1 expression remains incomplete. TheS. aureusexotoxin expression (Sae) operon contains a well-characterized two-component system that regulates a number of important exotoxins inS. aureus, although regulation of TSST-1 by the Sae system has not been investigated. We generated a defined deletion mutant of the Sae histidine kinase sensor (saeS) in the prototypic menstrual TSS strainS. aureusMN8. Mutation ofsaeSresulted in a complete loss of TSST-1 expression. Using both luciferase reporter experiments and quantitative real-time PCR, we demonstrate that the Sae system is an important transcriptional activator of TSST-1 expression. Recombinant SaeR was able to bind directly to thetstpromoter to a region containing two SaeR consensus binding sites. Although the stand-alone SarA transcriptional regulator has been shown to be both a positive and a negative regulator of TSST-1, deletion ofsarAinS. aureusMN8 resulted in a dramatic overexpression of TSST-1. As expected, mutation ofagralso reduced TSST-1 expression, but this phenotype appeared to be independent of Sae. A double mutation ofsaeSandsarAresulted in the loss of TSST-1 expression. This work indicates that the Sae system is a dominant and direct transcriptional activator that is required for expression of TSST-1.IMPORTANCEThe TSST-1 superantigen is an exotoxin, produced by some strains ofS. aureus, that has a clear role in both menstrual and nonmenstrual TSS. Although the well-characterizedagrquorum sensing system is a known positive regulator of TSST-1, the molecular mechanisms that directly control TSST-1 expression are only partially understood. Our studies demonstrate that the Sae two-component regulatory system is a positive transcriptional regulator that binds directly to the TSST-1 promoter, and furthermore, our data suggest that Sae is required for expression of TSST-1. This work highlights how major regulatory circuits can converge to fine-tune exotoxin expression and suggests that the Sae regulatory system may be an important target for antivirulence strategies.

scholarly journals CitAB Two-Component System-Regulated Citrate Utilization Contributes toVibrio choleraeCompetitiveness with the Gut Microbiota

2018 ◽  
Vol 87 (3) ◽  
Author(s):  
Ming Liu ◽  
Guijuan Hao ◽  
Zhe Li ◽  
Yitian Zhou ◽  
Reyna Garcia-Sillas ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Bacterial Species ◽  
Enteric Bacteria ◽  
Enteric Pathogens ◽  
Two Component System ◽  
Component System ◽  
Content Type ◽  
Two Component ◽  
Citrate Fermentation

ABSTRACTCitrate is a ubiquitous compound and can be utilized by many bacterial species, including enteric pathogens, as a carbon and energy source. Genes involved in citrate utilization have been extensively studied in some enteric bacteria, such asKlebsiella pneumoniae; however, their role in pathogenesis is still not clear. In this study, we investigated citrate utilization and regulation inVibrio cholerae, the causative agent of cholera. The putative anaerobic citrate fermentation genes inV. cholerae, consisting ofcitCDEFXG,citS-oadGAB, and the two-component system (TCS) genescitAB, are highly homologous to those inK. pneumoniae. Deletion analysis shows that thesecitgenes are essential forV. choleraegrowth when citrate is the sole carbon source. The expression ofcitCandcitSoperons was dependent on citrate and CitAB, whose transcription was autorepressed and regulated by another TCS regulator, ArcA. In addition, citrate fermentation was under the control of catabolite repression. Mouse colonization experiments showed thatV. choleraecan utilize citratein vivousing the citrate fermentation pathway and thatV. choleraelikely needs to compete with other members of the gut microbiota to access citrate in the gut.

scholarly journals Evidence of Robustness in a Two-Component System Using a Synthetic Circuit

2019 ◽  
Vol 202 (4) ◽  
Author(s):  
Arkajyoti Dutta ◽  
Paulami Rudra ◽  
Suman Kumar Banik ◽  
Jayanta Mukhopadhyay
Keyword(s):  
Signaling Pathway ◽  
Regulatory Networks ◽  
Sensor Kinase ◽  
Two Component System ◽  
Component System ◽  
Content Type ◽  
Two Component ◽  
Synthetic Circuit

ABSTRACT Variation in the concentration of biological components is inescapable for any cell. Robustness in any biological circuit acts as a cushion against such variation and enables the cells to produce homogeneous output despite the fluctuation. The two-component system (TCS) with a bifunctional sensor kinase (that possesses both kinase and phosphatase activities) is proposed to be a robust circuit. Few theoretical models explain the robustness of a TCS, although the criteria and extent of robustness by these models differ. Here, we provide experimental evidence to validate the extent of the robustness of a TCS signaling pathway. We have designed a synthetic circuit in Escherichia coli using a representative TCS of Mycobacterium tuberculosis, MprAB, and monitored the in vivo output signal by systematically varying the concentration of either of the components or both. We observed that the output of the TCS is robust if the concentration of MprA is above a threshold value. This observation is further substantiated by two in vitro assays, in which we estimated the phosphorylated MprA pool or MprA-dependent transcription yield by varying either of the components of the TCS. This synthetic circuit could be used as a model system to analyze the relationship among different components of gene regulatory networks. IMPORTANCE Robustness in essential biological circuits is an important feature of the living organism. A few pieces of evidence support the existence of robustness in vivo in the two-component system (TCS) with a bifunctional sensor kinase (SK). The assays were done under physiological conditions in which the SK was much lower than the response regulator (RR). Here, using a synthetic circuit, we varied the concentrations of the SK and RR of a representative TCS to monitor output robustness in vivo. In vitro assays were also performed under conditions where the concentration of the SK was greater than that of the RR. Our results demonstrate the extent of output robustness in the TCS signaling pathway with respect to the concentrations of the two components.

scholarly journals Nutritional Regulation of the Sae Two-Component System by CodY inStaphylococcus aureus

2018 ◽  
Vol 200 (8) ◽  
Author(s):  
Kevin D. Mlynek ◽  
William E. Sause ◽  
Derek E. Moormeier ◽  
Marat R. Sadykov ◽  
Kurt R. Hill ◽  
...  
Keyword(s):  
Gene Expression ◽  
Virulence Factors ◽  
Virulence Gene ◽  
Nutrient Depletion ◽  
Global Regulator ◽  
Two Component System ◽  
Component System ◽  
Content Type ◽  
Virulence Gene Expression ◽  
Two Component

ABSTRACTStaphylococcus aureussubverts innate defenses during infection in part by killing host immune cells to exacerbate disease. This human pathogen intercepts host cues and activates a transcriptional response via theS. aureusexoprotein expression (SaeR/SaeS [SaeR/S]) two-component system to secrete virulence factors critical for pathogenesis. We recently showed that the transcriptional repressor CodY adjusts nuclease (nuc) gene expression via SaeR/S, but the mechanism remained unknown. Here, we identified two CodY binding motifs upstream of thesaeP1 promoter, which suggested direct regulation by this global regulator. We show that CodY shares a binding site with the positive activator SaeR and that alleviating direct CodY repression at this site is sufficient to abrogate stochastic expression, suggesting that CodY repressessaeexpression by blocking SaeR binding. Epistasis experiments support a model that CodY also controlssaeindirectly through Agr and Rot-mediated repression of thesaeP1 promoter. We also demonstrate that CodY repression ofsaerestrains production of secreted cytotoxins that kill human neutrophils. We conclude that CodY plays a previously unrecognized role in controlling virulence gene expression via SaeR/S and suggest a mechanism by which CodY acts as a master regulator of pathogenesis by tying nutrient availability to virulence gene expression.IMPORTANCEBacterial mechanisms that mediate the switch from a commensal to pathogenic lifestyle are among the biggest unanswered questions in infectious disease research. Since the expression of most virulence genes is often correlated with nutrient depletion, this implies that virulence is a response to the lack of nourishment in host tissues and that pathogens likeS. aureusproduce virulence factors in order to gain access to nutrients in the host. Here, we show that specific nutrient depletion signals appear to be funneled to the SaeR/S system through the global regulator CodY. Our findings reveal a strategy by whichS. aureusdelays the production of immune evasion and immune-cell-killing proteins until key nutrients are depleted.

scholarly journals The Staphylococcus aureus KdpDE Two-Component System Couples Extracellular K+Sensing and Agr Signaling to Infection Programming

2011 ◽  
Vol 79 (6) ◽  
pp. 2154-2167 ◽  
Author(s):  
Ting Xue ◽  
Yibo You ◽  
De Hong ◽  
Haipeng Sun ◽  
Baolin Sun
Keyword(s):  
Staphylococcus Aureus ◽  
Uptake System ◽  
Main Function ◽  
Two Component System ◽  
Component System ◽  
Content Type ◽  
Two Component ◽  
Virulence Regulator ◽  
External K

ABSTRACTThe Kdp system is widely distributed among bacteria. InEscherichia coli, the Kdp-ATPase is a high-affinity K+uptake system and its expression is activated by the KdpDE two-component system in response to K+limitation or salt stress. However, information about the role of this system in many bacteria still remains obscure. Here we demonstrate that KdpFABC inStaphylococcus aureusis not a major K+transporter and that the main function of KdpDE is not associated with K+transport but that instead it regulates transcription for a series of virulence factors through sensing external K+concentrations, indicating that this bacterium might modulate its infectious status through sensing specific external K+stimuli in different environments. Our results further reveal thatS. aureusKdpDE is upregulated by the Agr/RNAIII system, which suggests that KdpDE may be an important virulence regulator coordinating the external K+sensing and Agr signaling during pathogenesis in this bacterium.

scholarly journals The CasKR Two-Component System Is Required for the Growth of Mesophilic and Psychrotolerant Bacillus cereus Strains at Low Temperatures

2014 ◽  
Vol 80 (8) ◽  
pp. 2493-2503 ◽  
Author(s):  
Sara Esther Diomandé ◽  
Stéphanie Chamot ◽  
Vera Antolinos ◽  
Florian Vasai ◽  
Marie-Hélène Guinebretière ◽  
...  
Keyword(s):  
Bacillus Cereus ◽  
Food Poisoning ◽  
Two Component System ◽  
Diverse Range ◽  
Component System ◽  
Content Type ◽  
Two Component ◽  
Temperature Ranges ◽  
Different Strains

ABSTRACTThe different strains ofBacillus cereuscan grow at temperatures covering a very diverse range. SomeB. cereusstrains can grow in chilled food and consequently cause food poisoning. We have identified a new sensor/regulator mechanism involved in low-temperatureB. cereusgrowth. Construction of a mutant of this two-component system enabled us to show that this system, called CasKR, is required for growth at the minimal temperature (Tmin). CasKR was also involved in optimal cold growth aboveTminand in cell survival belowTmin. Microscopic observation showed that CasKR plays a key role in cell shape during cold growth. Introducing thecasKRgenes in a ΔcasKRmutant restored its ability to grow atTmin. Although it was first identified in the ATCC 14579 model strain, this mechanism has been conserved in most strains of theB. cereusgroup. We show that the role of CasKR in cold growth is similar in otherB. cereus sensu latostrains with different growth temperature ranges, including psychrotolerant strains.

scholarly journals Identification of a Second Two-Component Signal Transduction System That Controls Fosfomycin Tolerance and Glycerol-3-Phosphate Uptake

2014 ◽  
Vol 197 (5) ◽  
pp. 861-871 ◽  
Author(s):  
Kumiko Kurabayashi ◽  
Yuko Hirakawa ◽  
Koichi Tanimoto ◽  
Haruyoshi Tomita ◽  
Hidetada Hirakawa
Keyword(s):  
Phosphate Uptake ◽  
Response Regulator ◽  
Anaerobic Respiration ◽  
Regulatory System ◽  
Carbon Substrate ◽  
Two Component System ◽  
Component System ◽  
Content Type ◽  
Two Component ◽  
Biological Cost

Particular interest in fosfomycin has resurfaced because it is a highly beneficial antibiotic for the treatment of refractory infectious diseases caused by pathogens that are resistant to other commonly used antibiotics. The biological cost to cells of resistance to fosfomycin because of chromosomal mutation is high. We previously found that a bacterial two-component system, CpxAR, induces fosfomycin tolerance in enterohemorrhagicEscherichia coli(EHEC) O157:H7. This mechanism does not rely on irreversible genetic modification and allows EHEC to relieve the fitness burden that results from fosfomycin resistance in the absence of fosfomycin. Here we show that another two-component system, TorSRT, which was originally characterized as a regulatory system for anaerobic respiration utilizing trimethylamine-N-oxide (TMAO), also induces fosfomycin tolerance. Activation of the Tor regulatory pathway by overexpression oftorR, which encodes the response regulator, or addition of TMAO increased fosfomycin tolerance in EHEC. We also show that phosphorylated TorR directly represses the expression ofglpT, a gene that encodes a symporter of fosfomycin and glycerol-3-phosphate, and activation of the TorR protein results in the reduced uptake of fosfomycin by cells. However, cells in which the Tor pathway was activated had an impaired growth phenotype when cultured with glycerol-3-phosphate as a carbon substrate. These observations suggest that the TorSRT pathway is the second two-component system to reversibly control fosfomycin tolerance and glycerol-3-phosphate uptake in EHEC, and this may be beneficial for bacteria by alleviating the biological cost. We expect that this mechanism could be a potential target to enhance the utility of fosfomycin as chemotherapy against multidrug-resistant pathogens.

scholarly journals The PedS2/PedR2 Two-Component System Is Crucial for the Rare Earth Element Switch inPseudomonas putidaKT2440

mSphere ◽  
2018 ◽  
Vol 3 (4) ◽  
Author(s):  
Matthias Wehrmann ◽  
Charlotte Berthelot ◽  
Patrick Billard ◽  
Janosch Klebensberger
Keyword(s):  
Rare Earth ◽  
Rare Earth Elements ◽  
Response Regulator ◽  
Regulatory Function ◽  
Methylotrophic Bacteria ◽  
Two Component System ◽  
Component System ◽  
Content Type ◽  
Two Component ◽  
Type Response

ABSTRACTInPseudomonas putidaKT2440, two pyrroloquinoline quinone-dependent ethanol dehydrogenases (PQQ-EDHs) are responsible for the periplasmic oxidation of a broad variety of volatile organic compounds (VOCs). Depending on the availability of rare earth elements (REEs) of the lanthanide series (Ln3+), we have recently reported that the transcription of the genes encoding the Ca2+-utilizing enzyme PedE and the Ln3+-utilizing enzyme PedH are inversely regulated. With adaptive evolution experiments, site-specific mutations, transcriptional reporter fusions, and complementation approaches, we now demonstrate that the PedS2/PedR2 (PP_2671/PP_2672) two-component system (TCS) plays a central role in the observed REE-mediated switch of PQQ-EDHs inP. putida. We provide evidence that in the absence of lanthanum (La3+), the sensor histidine kinase PedS2 phosphorylates its cognate LuxR-type response regulator PedR2, which in turn not only activatespedEgene transcription but is also involved in repression ofpedH. Our data further suggest that the presence of La3+lowers kinase activity of PedS2, either by the direct binding of the metal ions to the periplasmic region of PedS2 or by an uncharacterized indirect interaction, leading to reduced levels of phosphorylated PedR2. Consequently, the decreasingpedEexpression and concomitant alleviation ofpedHrepression causes—in conjunction with the transcriptional activation of thepedHgene by a yet unknown regulatory module—the Ln3+-dependent transition from PedE- to PedH-catalyzed oxidation of alcoholic VOCs.IMPORTANCEThe function of lanthanides for methanotrophic and methylotrophic bacteria is gaining increasing attention, while knowledge about the role of rare earth elements (REEs) in nonmethylotrophic bacteria is still limited. The present study investigates the recently described differential expression of the two PQQ-EDHs ofP. putidain response to lanthanides. We demonstrate that a specific TCS is crucial for their inverse regulation and provide evidence for a dual regulatory function of the LuxR-type response regulator involved. Thus, our study represents the first detailed characterization of the molecular mechanism underlying the REE switch of PQQ-EDHs in a nonmethylotrophic bacterium and stimulates subsequent investigations for the identification of additional genes or phenotypic traits that might be coregulated during REE-dependent niche adaptation.

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