2018
Lvr, a Signaling System That Controls Global Gene Regulation and Virulence in Pathogenic Leptospira
Adhikarla H, Wunder EA, Mechaly AE, Mehta S, Wang Z, Santos L, Bisht V, Diggle P, Murray G, Adler B, Lopez F, Townsend JP, Groisman E, Picardeau M, Buschiazzo A, Ko AI. Lvr, a Signaling System That Controls Global Gene Regulation and Virulence in Pathogenic Leptospira. Frontiers In Cellular And Infection Microbiology 2018, 8: 45. PMID: 29600195, PMCID: PMC5863495, DOI: 10.3389/fcimb.2018.00045.Peer-Reviewed Original ResearchConceptsResponse regulatorTwo-component system proteinsDNA-binding response regulatorGlobal transcriptional regulationHybrid histidine kinaseGlobal gene regulationNovel signal pathwayComprehensive genomic analysisPhosphotransfer assaysTCS genesHistidine kinaseGene duplicationTranscriptional regulationGene regulationCorresponding genesPhylogenetic analysisGenomic analysisMolecular basisMutant strainSystem proteinsSignaling systemInfection processGenesBranched pathwayVirulence
2017
Prioritization of polysaccharide utilization and control of regulator activation in Bacteroides thetaiotaomicron
Schwalm ND, Townsend GE, Groisman EA. Prioritization of polysaccharide utilization and control of regulator activation in Bacteroides thetaiotaomicron. Molecular Microbiology 2017, 104: 32-45. PMID: 28009067, DOI: 10.1111/mmi.13609.Peer-Reviewed Original ResearchConceptsBacteroides thetaiotaomicronGut symbiotic bacteriumSites of phosphorylationB. thetaiotaomicronDiauxic growthTwo-component systemResponse regulatorSensor kinaseMyriad of hostPolysaccharide utilizationUnaltered growthSymbiotic bacteriumMammalian gutSingle polypeptideMultiple polysaccharidesSingle polysaccharidePhosphorylationSpecific signalsPresence of glucoseThetaiotaomicronTranscriptionGenesBacteriumArabinanPolysaccharides
2012
Intramolecular arrangement of sensor and regulator overcomes relaxed specificity in hybrid two-component systems
Townsend GE, Raghavan V, Zwir I, Groisman EA. Intramolecular arrangement of sensor and regulator overcomes relaxed specificity in hybrid two-component systems. Proceedings Of The National Academy Of Sciences Of The United States Of America 2012, 110: e161-e169. PMID: 23256153, PMCID: PMC3545799, DOI: 10.1073/pnas.1212102110.Peer-Reviewed Original ResearchConceptsTwo-component regulatory systemResponse regulatorSensor kinasePhosphotransfer specificityRelaxed specificityTwo-component systemHuman gut symbiont Bacteroides thetaiotaomicronGut symbiont Bacteroides thetaiotaomicronRR pairsCognate response regulatorCognate protein partnersRegulatory systemProtein partnersTransduce signalsCellular processesSignal transductionSingle polypeptidePhosphoryl transferNoncognate proteinsBacteroides thetaiotaomicronSpecific interactionsRegulatorIntramolecular arrangementTransductionKinaseInhibition of Bacterial Virulence: Drug‐Like Molecules Targeting the Salmonella enterica PhoP Response Regulator
Tang YT, Gao R, Havranek JJ, Groisman EA, Stock AM, Marshall GR. Inhibition of Bacterial Virulence: Drug‐Like Molecules Targeting the Salmonella enterica PhoP Response Regulator. Chemical Biology & Drug Design 2012, 79: 1007-1017. PMID: 22339993, PMCID: PMC3445336, DOI: 10.1111/j.1747-0285.2012.01362.x.Peer-Reviewed Original ResearchConceptsTwo-component signal transductionResponse regulatorPhoP response regulatorHistidine kinaseBacterial virulenceGene expressionSensor histidine kinaseVirulence gene regulationSignal transduction systemSignal transduction pathwaysExpression of genesTCST systemsStructure-based virtual screeningGene regulationSignal transductionTranscription factorsTransduction pathwaysTransduction systemVirtual screeningBiophysical assaysAntibacterial developmentMode of actionExternal signalsRegulatorRegulatory system
2010
Orphan and hybrid two-component system proteins in health and disease
Raghavan V, Groisman EA. Orphan and hybrid two-component system proteins in health and disease. Current Opinion In Microbiology 2010, 13: 226-231. PMID: 20089442, PMCID: PMC2861427, DOI: 10.1016/j.mib.2009.12.010.Peer-Reviewed Original ResearchConceptsTwo-component systemResponse regulatorSensor kinaseTwo-component system proteinsGut symbiont Bacteroides thetaiotaomicronOpportunistic pathogen Pseudomonas aeruginosaResponse regulator domainCognate response regulatorPhosphorylation-independent mannerPathogen Pseudomonas aeruginosaRegulator domainEukaryotic hostsMembrane-bound regulatorsExpression programsExpression of enzymesPhosphorylated stateBiosynthetic enzymesStreptomyces speciesSingle polypeptideBacterial interactionsSystem proteinsBacteroides thetaiotaomicronEnzymatic propertiesRegulatorCertain sugars
2008
Signal integration in bacterial two-component regulatory systems
Mitrophanov AY, Groisman EA. Signal integration in bacterial two-component regulatory systems. Genes & Development 2008, 22: 2601-2611. PMID: 18832064, PMCID: PMC2751022, DOI: 10.1101/gad.1700308.Peer-Reviewed Original ResearchConceptsTwo-component systemResponse regulatorTwo-component regulatory systemSignal integrationBacterial signal transductionGram-negative bacteriaCellular processesSignal transductionPhosphorylated statePhosphorylation statePhysiological functionsSpecific functionsRegulatory systemBiochemical reactionsKey mediatorRegulatorPhosphorelayAntibiotic resistanceDifferent mechanismsSporulationTransductionStationary phaseDNABacteriaGramThe PhoQ/PhoP Regulatory Network of Salmonella enterica
Kato A, Groisman EA. The PhoQ/PhoP Regulatory Network of Salmonella enterica. Advances In Experimental Medicine And Biology 2008, 631: 7-21. PMID: 18792679, DOI: 10.1007/978-0-387-78885-2_2.Peer-Reviewed Original ResearchConceptsTwo-component regulatory systemPathogen Salmonella enterica serovar TyphimuriumEnteric pathogen Salmonella enterica serovar TyphimuriumDistinct expression levelsPhoQ/PhoPTwo-component systemSalmonella enterica serovar TyphimuriumBacterial cell surfacePhoQ proteinPhoP proteinResponse regulatorTranscriptional cascadeConnector proteinEnterica serovar TyphimuriumPromoter structureRegulatory networksTranscription factorsSalmonella genesRegulatory architectureSalmonella lifestyleMajor regulatorExpression propertiesCell surfaceModifies expressionRegulatory system
2004
Connecting two-component regulatory systems by a protein that protects a response regulator from dephosphorylation by its cognate sensor
Kato A, Groisman EA. Connecting two-component regulatory systems by a protein that protects a response regulator from dephosphorylation by its cognate sensor. Genes & Development 2004, 18: 2302-2313. PMID: 15371344, PMCID: PMC517523, DOI: 10.1101/gad.1230804.Peer-Reviewed Original ResearchMeSH KeywordsAllelesBacterial ProteinsBase SequenceGene Expression Regulation, BacterialMagnesiumMolecular Sequence DataPhosphorylationPromoter Regions, GeneticProtein Processing, Post-TranslationalProtein Structure, TertiarySalmonella entericaSignal TransductionTranscription FactorsTranscription, GeneticConceptsTwo-component systemResponse regulatorPhosphorylated formTwo-component regulatory systemTranscription of PmrAResponse regulator PmrAPhoP/PhoQPmrA/PmrBPmrA proteinTarget promotersCognate sensorProtein bindsSignal transductionCellular responsesDephosphorylationRegulatory systemPmrAProteinTranscriptionMultiple signalsRegulatorHigh affinityPmrA.Fundamental questionsPhoP
2003
Making informed decisions: regulatory interactions between two-component systems
Bijlsma JJ, Groisman EA. Making informed decisions: regulatory interactions between two-component systems. Trends In Microbiology 2003, 11: 359-366. PMID: 12915093, DOI: 10.1016/s0966-842x(03)00176-8.Peer-Reviewed Original ResearchConceptsTwo-component systemTwo-component regulatory systemPost-transcriptional mechanismsMultitude of stressesResponse regulatorBacterial adaptationRegulatory interactionsComplex nichePhosphoryl transferMolecular levelRegulatory systemSpecific signalsMultiple signalsPhosphorelayMultifaceted environmentNicheRegulatorBacteriaPhosphataseMechanismStressAdaptation
2000
Acetyl phosphate-dependent activation of a mutant PhoP response regulator that functions independently of its cognate sensor kinase11Edited by M. Gottesman
Chamnongpol S, Groisman E. Acetyl phosphate-dependent activation of a mutant PhoP response regulator that functions independently of its cognate sensor kinase11Edited by M. Gottesman. Journal Of Molecular Biology 2000, 300: 291-305. PMID: 10873466, DOI: 10.1006/jmbi.2000.3848.Peer-Reviewed Original ResearchMeSH KeywordsAllelesAmino Acid SubstitutionBacterial ProteinsEnvironmentGene Expression Regulation, BacterialGenes, BacterialGenes, RegulatorMagnesiumMembrane ProteinsMethyl-Accepting Chemotaxis ProteinsModels, MolecularMutationOperonOrganophosphatesPhosphorylationProtein BindingProtein BiosynthesisProtein Structure, TertiaryRecombinant Fusion ProteinsSalmonella entericaTrans-ActivatorsTranscription, GeneticConceptsTranscription of PhoPResponse regulatorAcetyl phosphateResponse regulator receiver domainSites of phosphorylationVirulence gene expressionPhoP response regulatorTwo-component systemPhoQ proteinPhoP proteinReceiver domainSensor kinaseTranscriptional repressionCognate sensorMutant proteinsM. GottesmanPhosphorylated stateAspartate residueGene expressionPhoPTranscriptionPhosphate donorRegulatorProteinSalmonella enterica
1996
Two-component regulatory systems can interact to process multiple environmental signals
Soncini FC, Groisman EA. Two-component regulatory systems can interact to process multiple environmental signals. Journal Of Bacteriology 1996, 178: 6796-6801. PMID: 8955299, PMCID: PMC178578, DOI: 10.1128/jb.178.23.6796-6801.1996.Peer-Reviewed Original ResearchConceptsTwo-component systemPmrA/PmrB systemTwo-component regulatory systemMultiple environmental signalsPhoP/PhoQAcid-mediated activationPmrA proteinPhoQ proteinResponse regulatorTranscriptional regulationEnvironmental signalsEnvironmental cuesTranscriptionLociRegulatory systemVirulence determinantsGenesProteinPathogenic bacteriaPhoPMild acidificationPmrASalmonella typhimuriumBroad spectrumPhoQ