2020
Horizontally acquired regulatory gene activates ancestral regulatory system to promote Salmonella virulence
Choi J, Groisman EA. Horizontally acquired regulatory gene activates ancestral regulatory system to promote Salmonella virulence. Nucleic Acids Research 2020, 48: 10832-10847. PMID: 33045730, PMCID: PMC7641745, DOI: 10.1093/nar/gkaa813.Peer-Reviewed Original ResearchConceptsPhoP/PhoQAncestral regulatorNucleoid structuring protein H-NSProtein H-NSS. bongoriSalmonella enterica serovar TyphimuriumAncestral genomesH-NSTarget promotersEnterica serovar TyphimuriumRegulatory genesBacterial virulenceSalmonella virulencePromoter regionSsrBOpposite regulationGenesS. typhimuriumPhoQRegulatory systemSerovar TyphimuriumVirulenceTranscriptionPromoterRegulator
2015
Flagella-independent surface motility in Salmonella enterica serovar Typhimurium
Park SY, Pontes MH, Groisman EA. Flagella-independent surface motility in Salmonella enterica serovar Typhimurium. Proceedings Of The National Academy Of Sciences Of The United States Of America 2015, 112: 1850-1855. PMID: 25624475, PMCID: PMC4330729, DOI: 10.1073/pnas.1422938112.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine TriphosphatasesAmino Acid SequenceBacterial ProteinsBase SequenceCation Transport ProteinsComputational BiologyFlagellaGene Expression Regulation, BacterialMagnesiumMembrane Transport ProteinsMitochondrial Proton-Translocating ATPasesMolecular Sequence DataMovementMutagenesisSalmonella typhimuriumSequence AlignmentSequence Analysis, DNAConceptsSalmonella enterica serovar TyphimuriumEnterica serovar TyphimuriumPhoP/PhoQ regulatory systemMgtC mutantFlagellum-independent mannerFlagella-mediated motilitySerovar TyphimuriumForm of motilityWild-type SalmonellaNull mutantsMultiprotein complexesMgtC proteinF1Fo-ATPaseHeterologous promoterSmall proteinsUnknown functionProteinase K treatmentSurface motilityMgtAMutantsGroup motilityAllelic formsRegulatory systemBacterial replicationGenes
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 arrangementTransductionKinaseReciprocal Control between a Bacterium's Regulatory System and the Modification Status of Its Lipopolysaccharide
Kato A, Chen HD, Latifi T, Groisman EA. Reciprocal Control between a Bacterium's Regulatory System and the Modification Status of Its Lipopolysaccharide. Molecular Cell 2012, 47: 897-908. PMID: 22921935, PMCID: PMC3465083, DOI: 10.1016/j.molcel.2012.07.017.Peer-Reviewed Original ResearchInhibition 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
2009
Activated by Different Signals, the PhoP/PhoQ Two-Component System Differentially Regulates Metal Uptake
Choi E, Groisman EA, Shin D. Activated by Different Signals, the PhoP/PhoQ Two-Component System Differentially Regulates Metal Uptake. Journal Of Bacteriology 2009, 191: 7174-7181. PMID: 19801407, PMCID: PMC2786564, DOI: 10.1128/jb.00958-09.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine TriphosphatasesBacterial ProteinsBiological TransportBlotting, WesternCation Transport ProteinsGene Expression Regulation, BacterialHydrogen-Ion ConcentrationMagnesiumMembrane Transport ProteinsMetalsPhosphorylationReverse Transcriptase Polymerase Chain ReactionSalmonella typhimuriumConceptsPhoP/PhoQ systemPhoP/PhoQTwo-component systemTwo-component regulatory systemMgtA genePhoP proteinVirulence functionsMgtA transcriptionSalmonella genesLeader regionTransporter geneBiological consequencesGenesRegulatory systemAntimicrobial peptidesDistinct setsPhoQTranscriptionMetal uptakeSalmonella entericaMultiple signalsProteinExpressionPhoPMgtA
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
2007
A connector of two-component regulatory systems promotes signal amplification and persistence of expression
Kato A, Mitrophanov AY, Groisman EA. A connector of two-component regulatory systems promotes signal amplification and persistence of expression. Proceedings Of The National Academy Of Sciences Of The United States Of America 2007, 104: 12063-12068. PMID: 17615238, PMCID: PMC1924540, DOI: 10.1073/pnas.0704462104.Peer-Reviewed Original ResearchConceptsTwo-component regulatory systemBacterial signal transductionRegulatory systemPersistence of expressionSignal transductionGene transcriptionRegulatory architectureSmall proteinsSalmonella entericaPathwayFunctional characteristicsPmrDExpressionFunctional propertiesPhoP.AmplificationTranscriptionSignal amplificationTransductionGenesDominant formOrganismsProteinPersistenceEnterica[18] Gene Promoter Scan Methodology for Identifying and Classifying Coregulated Promoters
Zwir I, Harari O, Groisman EA. [18] Gene Promoter Scan Methodology for Identifying and Classifying Coregulated Promoters. Methods In Enzymology 2007, 422: 361-385. PMID: 17628149, PMCID: PMC3755887, DOI: 10.1016/s0076-6879(06)22018-4.Peer-Reviewed Original ResearchConceptsCoregulated promotersTwo-component regulatory systemCis-acting regulatory elementsDistinct regulatory networksSingle transcription factorPhoP/PhoQPhoP proteinGenomic approachesCoregulated genesPhoP regulonRegulatory networksRegulatory interactionsTranscription factorsRegulatory featuresGene transcriptionRegulatory elementsPostgenomic eraNovel memberDifferential expressionGenesEscherichia coliRegulatory systemSalmonella entericaPromoterMultiple mechanisms
2006
Acid pH activation of the PmrA/PmrB two‐component regulatory system of Salmonella enterica
Perez JC, Groisman EA. Acid pH activation of the PmrA/PmrB two‐component regulatory system of Salmonella enterica. Molecular Microbiology 2006, 63: 283-293. PMID: 17229213, PMCID: PMC1804205, DOI: 10.1111/j.1365-2958.2006.05512.x.Peer-Reviewed Original ResearchConceptsGlutamic acid residuesPmrA/PmrB systemAcid residuesTwo-component regulatory systemPathogen Salmonella enterica serovar TyphimuriumResponse regulator PmrATranscription of genesPmrA/PmrBSalmonella enterica serovar TyphimuriumPmrA proteinPolymyxin B resistancePeriplasmic domainWild-type SalmonellaEnterica serovar TyphimuriumGene productsGene expressionAnimal hostsRegulatory systemB resistanceSerovar TyphimuriumTranscriptionSalmonella entericaCellular changesGenesPH activation
2005
The PhoP/PhoQ system controls the intramacrophage type three secretion system of Salmonella enterica
Bijlsma JJ, Groisman EA. The PhoP/PhoQ system controls the intramacrophage type three secretion system of Salmonella enterica. Molecular Microbiology 2005, 57: 85-96. PMID: 15948951, DOI: 10.1111/j.1365-2958.2005.04668.x.Peer-Reviewed Original ResearchConceptsSPI-2 pathogenicity islandPhoP/PhoQ systemType three secretion systemThree secretion systemPhoP proteinSecretion systemSsa genesPathogenicity islandTwo-component regulatory systemResponse regulator SsrBPhoP/PhoQRegulatory systemTwo-component systemSalmonella entericaEukaryotic cellsChromatin immunoprecipitationCentral roleDifferent regulatory systemsSalmonella virulenceUntranslated regionDistinct signalsPhoPGenesEffectorsProteinDissecting the PhoP regulatory network of Escherichia coli and Salmonella enterica
Zwir I, Shin D, Kato A, Nishino K, Latifi T, Solomon F, Hare JM, Huang H, Groisman EA. Dissecting the PhoP regulatory network of Escherichia coli and Salmonella enterica. Proceedings Of The National Academy Of Sciences Of The United States Of America 2005, 102: 2862-2867. PMID: 15703297, PMCID: PMC548500, DOI: 10.1073/pnas.0408238102.Peer-Reviewed Original ResearchConceptsRegulatory networksEnteric bacteria Escherichia coliDistinct regulatory networksEscherichia coliPhoP/PhoQTwo-component systemSalmonella entericaCoregulated promotersPhoP proteinGenomic approachesPhoP regulonPromoter featuresRegulatory featuresGene transcriptionGene expressionBacteria Escherichia coliRegulatory systemGenesMultiple mechanismsColiResistance determinantsEntericaRegulonPhoQTranscription
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 questionsPhoPThe PmrA-Regulated pmrC Gene Mediates Phosphoethanolamine Modification of Lipid A and Polymyxin Resistance in Salmonella enterica
Lee H, Hsu FF, Turk J, Groisman EA. The PmrA-Regulated pmrC Gene Mediates Phosphoethanolamine Modification of Lipid A and Polymyxin Resistance in Salmonella enterica. Journal Of Bacteriology 2004, 186: 4124-4133. PMID: 15205413, PMCID: PMC421605, DOI: 10.1128/jb.186.13.4124-4133.2004.Peer-Reviewed Original ResearchConceptsPolymyxin B resistancePmrA mutantB resistanceInner membrane proteinLarge periplasmic regionLipid AN-terminal regionPmrC genePhosphoethanolamine modificationSalmonella entericaPeriplasmic regionTransmembrane domainDouble mutantEnzymatic domainsMembrane proteinsGene resultsAminoarabinose modificationMutantsGenesRegulatory systemAminoarabinosePmrAPolymyxin resistanceProteinAntibiotic polymyxin B
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 environmentNicheRegulatorBacteriaPhosphataseMechanismStressAdaptationMg2+ Sensing by the Mg2+ Sensor PhoQ of Salmonella enterica
Chamnongpol S, Cromie M, Groisman EA. Mg2+ Sensing by the Mg2+ Sensor PhoQ of Salmonella enterica. Journal Of Molecular Biology 2003, 325: 795-807. PMID: 12507481, DOI: 10.1016/s0022-2836(02)01268-8.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAmino Acid SubstitutionBacterial ProteinsBase SequenceBinding SitesConserved SequenceDNA, BacterialMagnesiumMolecular Sequence DataMutagenesis, Site-DirectedPhosphorylationProtein Structure, TertiaryRecombinant ProteinsSalmonella entericaSequence Homology, Amino AcidTranscription, GeneticConceptsTranscription of PhoPPhoQ proteinSensor PhoQPeriplasmic domainTwo-component regulatory systemResponse regulator PhoPExpression of phoPPhoP/PhoQWild-type responseWild-type abilityAmino acid residuesGram-negative speciesRegulator PhoPGene transcriptionPhoPAcid residuesTranscriptionHistidine residuesPhoQGenesAcetyl phosphateRegulatory systemProteinMutantsSalmonella enterica
2000
The regulatory protein PhoP controls susceptibility to the host inflammatory response in Shigella flexneri
Moss J, Fisher P, Vick B, Groisman E, Zychlinsky A. The regulatory protein PhoP controls susceptibility to the host inflammatory response in Shigella flexneri. Cellular Microbiology 2000, 2: 443-452. PMID: 11207599, DOI: 10.1046/j.1462-5822.2000.00065.x.Peer-Reviewed Original ResearchConceptsWild-type strainPhoP mutantPhoP/PhoQ systemTwo-component regulatory systemRegulatory protein PhoPHost cell phagosomesPhoP/PhoQKey virulence genesMutant bacteriaEnteric bacteriumPathogen escapeCell phagosomesHost cellsMutantsWild-type ShigellaPolymorphonuclear leucocytesRegulatory systemVirulence genesAntimicrobial moleculesAntimicrobial peptidesPhoPExtreme acidInflammatory responseEpithelial cellsPhagosomes
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 spectrumPhoQMg2+ as an Extracellular Signal: Environmental Regulation of Salmonella Virulence
Véscovi E, Soncini F, Groisman E. Mg2+ as an Extracellular Signal: Environmental Regulation of Salmonella Virulence. Cell 1996, 84: 165-174. PMID: 8548821, DOI: 10.1016/s0092-8674(00)81003-x.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceBacterial ProteinsBase SequenceCationsGene Expression Regulation, BacterialHydrogen-Ion ConcentrationKineticsMagnesiumMolecular Sequence DataMutationPeptidesPhenotypeProtein ConformationSalmonella typhimuriumSensitivity and SpecificitySignal TransductionTranscription FactorsVirulenceConceptsPhoP/PhoQ systemTranscription of PhoPSignal transduction cascadeVirulence regulatory systemGene expression patternsPeriplasmic domainWild-type SalmonellaExtracellular signalsTransduction cascadeSalmonella virulenceExpression patternsFirst messengersPhoPRegulatory systemGenesPhoQSalmonella typhimuriumPhysiological concentrationsDivalent cationsTranscriptionConcentration of Mg2LociMg2DomainVirulence