2021
How the PhoP/PhoQ System Controls Virulence and Mg2+ Homeostasis: Lessons in Signal Transduction, Pathogenesis, Physiology, and Evolution
Groisman EA, Duprey A, Choi J. How the PhoP/PhoQ System Controls Virulence and Mg2+ Homeostasis: Lessons in Signal Transduction, Pathogenesis, Physiology, and Evolution. Microbiology And Molecular Biology Reviews 2021, 85: 10.1128/mmbr.00176-20. PMID: 34191587, PMCID: PMC8483708, DOI: 10.1128/mmbr.00176-20.Peer-Reviewed Original ResearchConceptsPhoP/PhoQ systemPhoP/PhoQSignal transductionAbundance of hundredsGram-negative bacterial speciesTwo-component systemSalmonella enterica serovar TyphimuriumRegulatory RNAsEnterica serovar TyphimuriumTranscription factorsProtease regulatorsTranscriptional effectsCationic antimicrobial peptidesInducing conditionsBacterial speciesSerovar TyphimuriumPhysiological consequencesAntimicrobial peptidesPhoQTransductionVirulenceHomeostasisAbundanceNovel formPhoP
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
2013
The Biology of the PmrA/PmrB Two-Component System: The Major Regulator of Lipopolysaccharide Modifications
Chen HD, Groisman EA. The Biology of the PmrA/PmrB Two-Component System: The Major Regulator of Lipopolysaccharide Modifications. Annual Review Of Microbiology 2013, 67: 83-112. PMID: 23799815, PMCID: PMC8381567, DOI: 10.1146/annurev-micro-092412-155751.Peer-Reviewed Original ResearchConceptsPmrA/PmrBTwo-component systemPmrA/PmrB systemMajor regulatorEnteric pathogen Salmonella entericaGene expression outputPathogen Salmonella entericaTranscriptional regulatorsExpression outputEcological nichesOuter membraneRelated bacteriaLPS modificationsExtent bacteriaLipopolysaccharide modificationDifferential survivalRegulatorHost immune systemNegative bacteriaSalmonella entericaBacteriaBiologyPmrBQuantitative differencesImmune system
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 arrangementTransductionKinase
2011
Ancestral Genes Can Control the Ability of Horizontally Acquired Loci to Confer New Traits
Chen HD, Jewett MW, Groisman EA. Ancestral Genes Can Control the Ability of Horizontally Acquired Loci to Confer New Traits. PLOS Genetics 2011, 7: e1002184. PMID: 21811415, PMCID: PMC3140997, DOI: 10.1371/journal.pgen.1002184.Peer-Reviewed Original ResearchMeSH KeywordsAnti-Bacterial AgentsBacterial ProteinsDNA, BacterialDrug Resistance, BacterialEscherichia coliEscherichia coli ProteinsGene Expression Regulation, BacterialGene Transfer, HorizontalKineticsMagnesiumMolecular Sequence DataPhosphorylationPolymyxin BReverse Transcriptase Polymerase Chain ReactionSalmonella typhimuriumSequence Analysis, DNATranscription FactorsTransformation, BacterialConceptsGene productsPmrD proteinPmrA/PmrB systemSpecies-specific traitsPmrA/PmrBE. coliHigh phosphatase activityBacterium Escherichia coliTwo-component systemPmrA proteinPolymyxin B resistanceAncestral locusAncestral proteinAncestral geneAncestral pathwayNew traitsBiochemical activityDifferent speciesGenesPmrB proteinEscherichia coliPhosphatase activityB resistanceProteinSalmonella enterica
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
2009
Response Acceleration in Post-translationally Regulated Genetic Circuits
Mitrophanov AY, Groisman EA. Response Acceleration in Post-translationally Regulated Genetic Circuits. Journal Of Molecular Biology 2009, 396: 1398-1409. PMID: 19932119, PMCID: PMC2861412, DOI: 10.1016/j.jmb.2009.11.043.Peer-Reviewed Original ResearchConceptsRegulatory proteinsTwo-component system familyBacterial signal transductionGenetic regulatory circuitsTwo-component systemSteady-state output levelGenetic circuitsRegulatory circuitsSignal transductionSensor proteinsTranscription factorsGene expressionLiving cellsPhosphorylation levelsProteinSpecific signalsKinetic propertiesSuch modificationsCellsTransductionPhosphorylationRegulatorMechanismPrevalent formExpressionActivated 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
2006
The PhoP/PhoQ two-component system stabilizes the alternative sigma factor RpoS in Salmonella enterica
Tu X, Latifi T, Bougdour A, Gottesman S, Groisman EA. The PhoP/PhoQ two-component system stabilizes the alternative sigma factor RpoS in Salmonella enterica. Proceedings Of The National Academy Of Sciences Of The United States Of America 2006, 103: 13503-13508. PMID: 16938894, PMCID: PMC1557385, DOI: 10.1073/pnas.0606026103.Peer-Reviewed Original ResearchConceptsSigma factor RpoSPhoP/PhoQTwo-component systemAlternative sigma factor RpoSTwo-component regulatory system PhoP/PhoQPhoP/PhoQ.Stress response genesSalmonella enterica serovar TyphimuriumRpoS stabilityClpXP proteaseTranscriptional activatorEnterica serovar TyphimuriumRegulatory circuitsRpoS mutantResponse genesRegulatory proteinsProtein turnoverRpoSBacterial speciesEscherichia coliPhoP geneGenesSerovar TyphimuriumE. coliPhoQThe PmrA/PmrB and RcsC/YojN/RcsB systems control expression of the Salmonella O‐antigen chain length determinant
Delgado MA, Mouslim C, Groisman EA. The PmrA/PmrB and RcsC/YojN/RcsB systems control expression of the Salmonella O‐antigen chain length determinant. Molecular Microbiology 2006, 60: 39-50. PMID: 16556219, DOI: 10.1111/j.1365-2958.2006.05069.x.Peer-Reviewed Original ResearchConceptsPmrA/PmrBO-antigen subunitSame start siteHydrophobic lipid ASDS/PAGE gelsChain length determinantTwo-component systemSalmonella enterica serovar TyphimuriumO-antigenGram-negative bacteriaNull mutantsEnterica serovar TyphimuriumStart siteRcsB mutantDifferent environmental conditionsCell envelopeRegulatory proteinsLPS genesOutermost componentCore oligosaccharideSerovar TyphimuriumGenesEnvironmental conditionsPAGE gelsRcsB
2005
Virulence and drug resistance roles of multidrug efflux systems of Salmonella enterica serovar Typhimurium
Nishino K, Latifi T, Groisman EA. Virulence and drug resistance roles of multidrug efflux systems of Salmonella enterica serovar Typhimurium. Molecular Microbiology 2005, 59: 126-141. PMID: 16359323, DOI: 10.1111/j.1365-2958.2005.04940.x.Peer-Reviewed Original ResearchConceptsDrug efflux systemsEfflux systemSalmonella virulenceEscherichia coli homologueToxic compound extrusionResponse regulator PhoPATP-binding cassette (ABC) superfamiliesPhoP/PhoQOuter membrane componentsAmino acid sequenceDrug resistance rolesTwo-component systemSalmonella enterica serovar TyphimuriumGram-negative speciesMultidrug efflux systemsSame operonEnterica serovar TyphimuriumRegulator PhoPCompound extrusionAcid sequenceMajor facilitatorEfflux system genesPromoter regionVirulence phenotypesMajor regulatorThe 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
Phenotypic differences between Salmonella and Escherichia coli resulting from the disparate regulation of homologous genes
Winfield MD, Groisman EA. Phenotypic differences between Salmonella and Escherichia coli resulting from the disparate regulation of homologous genes. Proceedings Of The National Academy Of Sciences Of The United States Of America 2004, 101: 17162-17167. PMID: 15569938, PMCID: PMC534605, DOI: 10.1073/pnas.0406038101.Peer-Reviewed Original ResearchConceptsPmrD proteinPolymyxin B resistanceHomologous genesB resistancePhenotypic differencesDifferential regulationRange of nichesSpecies-specific genesPmrA/PmrBE. coliE. coli KTwo-component systemEnterica serovar TyphimuriumGene transcriptionS. enterica serovar TyphimuriumEcological consequencesColi KLPS modificationsNatural isolatesPathogenicity islandE. coli strainsGenesMolecular analysisEscherichia coliSerovar TyphimuriumConnecting 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 questionsPhoPTranscriptional Control of the Antimicrobial Peptide Resistance ugtL Gene by the Salmonella PhoP and SlyA Regulatory Proteins*
Shi Y, Latifi T, Cromie MJ, Groisman EA. Transcriptional Control of the Antimicrobial Peptide Resistance ugtL Gene by the Salmonella PhoP and SlyA Regulatory Proteins*. Journal Of Biological Chemistry 2004, 279: 38618-38625. PMID: 15208313, DOI: 10.1074/jbc.m406149200.Peer-Reviewed Original ResearchMeSH KeywordsAntimicrobial Cationic PeptidesBacterial ProteinsBase SequenceBeta-GalactosidaseBinding SitesBlotting, SouthernDeoxyribonuclease IGene Expression Regulation, BacterialMagaininsMagnesiumMembrane ProteinsModels, BiologicalMolecular Sequence DataMutationPeptidesPlasmidsPolymyxin BPromoter Regions, GeneticProtein BindingSalmonellaSingle-Strand Specific DNA and RNA EndonucleasesTranscription FactorsTranscription, GeneticTranscriptional ActivationXenopus ProteinsConceptsPhoP proteinSlyA mutantSlyA proteinPhoP/PhoQTranscription start siteAntimicrobial peptidesTwo-component systemMagainin 2Transcriptional activatorAbility of SalmonellaTranscriptional controlStart siteMaster regulatorRegulatory proteinsTranscriptionVirulence attenuationAntimicrobial peptide magainin 2PhoPGenesProteinPromoterMutantsSlyA.PhoQPeptides
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 environmentNicheRegulatorBacteriaPhosphataseMechanismStressAdaptationClosing the loop: The PmrA/PmrB two-component system negatively controls expression of its posttranscriptional activator PmrD
Kato A, Latifi T, Groisman EA. Closing the loop: The PmrA/PmrB two-component system negatively controls expression of its posttranscriptional activator PmrD. Proceedings Of The National Academy Of Sciences Of The United States Of America 2003, 100: 4706-4711. PMID: 12676988, PMCID: PMC153620, DOI: 10.1073/pnas.0836837100.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceArtificial Gene FusionBacterial ProteinsBase SequenceBinding SitesDNA, BacterialFeedbackGene Expression Regulation, BacterialGenes, BacterialModels, GeneticMolecular Sequence DataMutationPlasmidsPromoter Regions, GeneticProtein BindingSalmonella typhimuriumTranscription FactorsConceptsPmrA proteinTwo-component systemResponse regulator PmrAAppropriate cellular responsesPmrA/PmrBPhoQ proteinPhoP proteinRegulatory circuitsPosttranscriptional levelPromoter upstreamNegative regulationCellular responsesPmrB proteinCellular levelProteinPmrASalmonella entericaGenesMultiple signalsPmrDFeedback loopSingular exampleExpressionPhoPFundamental questions