2020
FEDS: a Novel Fluorescence-Based High-Throughput Method for Measuring DNA Supercoiling In Vivo
Duprey A, Groisman EA. FEDS: a Novel Fluorescence-Based High-Throughput Method for Measuring DNA Supercoiling In Vivo. MBio 2020, 11: 10.1128/mbio.01053-20. PMID: 32723920, PMCID: PMC7387798, DOI: 10.1128/mbio.01053-20.Peer-Reviewed Original ResearchConceptsDNA supercoilingFluorescent proteinDNA supercoiling resultsBacterial DNA supercoilingSingle-cell heterogeneityGreen fluorescent proteinRed fluorescent proteinCellular physiologyDNA processesHigh-throughput methodConstitutive promoterNovel regulatorNucleotide sequenceGenetic informationRegulatory loopHigh-throughput measurementsSupercoilingForms of lifeGenesSingle cellsTranscriptionPromoterProteinChemical supportNovel fluorescenceThe phosphorelay BarA/SirA activates the non-cognate regulator RcsB in Salmonella enterica
Salvail H, Groisman EA. The phosphorelay BarA/SirA activates the non-cognate regulator RcsB in Salmonella enterica. PLOS Genetics 2020, 16: e1008722. PMID: 32392214, PMCID: PMC7241856, DOI: 10.1371/journal.pgen.1008722.Peer-Reviewed Original ResearchConceptsBarA/SirACell wall perturbationSet of genesBacterium Salmonella enterica serovar TyphimuriumOuter-membrane stressSalmonella enterica serovar TyphimuriumPhosphorelay proteinsPhosphorelay systemLuria-Bertani mediumEnterica serovar TyphimuriumRcsBEnvironmental stressGene transcriptionGene expressionWall perturbationDifferent regulatorsSpectrum of environmentsPhosphorelaySerovar TyphimuriumRegulatorRcsCProteinTranscriptionSalmonella entericaGenes
2019
The expanded specificity and physiological role of a widespread N-degron recognin
Gao X, Yeom J, Groisman EA. The expanded specificity and physiological role of a widespread N-degron recognin. Proceedings Of The National Academy Of Sciences Of The United States Of America 2019, 116: 18629-18637. PMID: 31451664, PMCID: PMC6744884, DOI: 10.1073/pnas.1821060116.Peer-Reviewed Original ResearchConceptsN-degron pathwayN-terminusLarge hydrophobic amino acidsPhysiological roleAmino acidsN-terminal methionineFourth amino acidHydrophobic amino acidsProtease ClpAPClp proteinsProtein homeostasisProteolytic systemIntact proteinProteinTerminusPathwayClpAPDegronAlarmoneStrong preferenceOrganellesBindsBacteriumHomeostasisProteaseActivator of one protease transforms into inhibitor of another in response to nutritional signals
Yeom J, Groisman EA. Activator of one protease transforms into inhibitor of another in response to nutritional signals. Genes & Development 2019, 33: 1280-1292. PMID: 31371438, PMCID: PMC6719616, DOI: 10.1101/gad.325241.119.Peer-Reviewed Original ResearchConceptsNutritional signalsProtease specificityClpAP proteaseProtease LonProtein homeostasisParticular proteinToxic proteinsRegulatory roleParticular substrateRapid response mechanismProtein amountSpecific signalsResponse mechanismsProteaseProteinActivatorAcetylationProteomeCellsInhibitorsLonAdaptorSpecificityProteolysisBindsSlow growth determines nonheritable antibiotic resistance in Salmonella enterica
Pontes MH, Groisman EA. Slow growth determines nonheritable antibiotic resistance in Salmonella enterica. Science Signaling 2019, 12 PMID: 31363068, PMCID: PMC7206539, DOI: 10.1126/scisignal.aax3938.Peer-Reviewed Original ResearchConceptsToxin-antitoxin modulesSlow growthGenetic repertoireSuch proteinsPersister formationAntibiotic-resistant mutantsParticular proteinPersister statePhysiological processesPersistent bacteriaPhenotypic changesBacterial populationsCell growthUse of antibioticsSalmonella entericaBactericidal antibioticsBacteriaProteinSmall subpopulationAbundanceUnderlying physiological processesAntibiotic resistanceGrowthMutantsOpposite changes
2014
Unusually long-lived pause required for regulation of a Rho-dependent transcription terminator
Hollands K, Sevostiyanova A, Groisman EA. Unusually long-lived pause required for regulation of a Rho-dependent transcription terminator. Proceedings Of The National Academy Of Sciences Of The United States Of America 2014, 111: e1999-e2007. PMID: 24778260, PMCID: PMC4024889, DOI: 10.1073/pnas.1319193111.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine TriphosphatasesBacterial ProteinsBase SequenceDNA-Directed RNA PolymerasesGene Expression Regulation, BacterialMagnesiumMembrane Transport ProteinsMolecular Sequence DataNucleic Acid ConformationRho FactorRiboswitchRNA, BacterialRNA, MessengerSalmonella entericaTerminator Regions, GeneticConceptsRho-dependent terminationRho-dependent terminatorsRho-dependent transcription terminatorsTranscription termination eventsTermination eventsTranscription terminationTranscription terminatorPause sitesSuch terminatorsSequence elementsAcid sequenceLeader regionNucleic acid sequencesMolecular determinantsSpecific signalsTerminatorRemarkable longevitySalmonella entericaRhoRegulationSingle site
2012
An Allele of an Ancestral Transcription Factor Dependent on a Horizontally Acquired Gene Product
Chen HD, Jewett MW, Groisman EA. An Allele of an Ancestral Transcription Factor Dependent on a Horizontally Acquired Gene Product. PLOS Genetics 2012, 8: e1003060. PMID: 23300460, PMCID: PMC3531487, DOI: 10.1371/journal.pgen.1003060.Peer-Reviewed Original ResearchConceptsPolymyxin B resistanceGene productsTranscription of PmrAGene regulatory circuitsB resistanceSingle amino acid differenceAmino acid differencesPmrA proteinAncestral genomesAncestral genePmrD proteinRegulatory circuitsB alleleHorizontal transferGene expressionPhenotypic differencesAcid differencesGenesBiochemical propertiesBiofilm formationPmrAAllelesSalmonella entericaS. entericaProteinInhibition 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
Positive Autoregulation Shapes Response Timing and Intensity in Two-component Signal Transduction Systems
Mitrophanov AY, Hadley TJ, Groisman EA. Positive Autoregulation Shapes Response Timing and Intensity in Two-component Signal Transduction Systems. Journal Of Molecular Biology 2010, 401: 671-680. PMID: 20600106, PMCID: PMC2942797, DOI: 10.1016/j.jmb.2010.06.051.Peer-Reviewed Original Research
2009
Transcription factor function and promoter architecture govern the evolution of bacterial regulons
Perez JC, Groisman EA. Transcription factor function and promoter architecture govern the evolution of bacterial regulons. Proceedings Of The National Academy Of Sciences Of The United States Of America 2009, 106: 4319-4324. PMID: 19251636, PMCID: PMC2649204, DOI: 10.1073/pnas.0810343106.Peer-Reviewed Original ResearchConceptsRegulatory circuitsBacterial regulonsPhoP proteinRegulatory protein PhoPBacterial transcription factorsTranscription factor functionCis-regulatory elementsGene regulatory circuitsHorizontal gene transferPathogen Salmonella entericaPromoter architectureEvolutionary changeRelated organismsVirulence regulatorTranscription factorsRegulonPhenotypic differencesFactor functionGene transferYersinia pestisSalmonella entericaCore membersProteinEukaryotesPhoP
2008
RstA-Promoted Expression of the Ferrous Iron Transporter FeoB under Iron-Replete Conditions Enhances Fur Activity in Salmonella enterica
Jeon J, Kim H, Yun J, Ryu S, Groisman EA, Shin D. RstA-Promoted Expression of the Ferrous Iron Transporter FeoB under Iron-Replete Conditions Enhances Fur Activity in Salmonella enterica. Journal Of Bacteriology 2008, 190: 7326-7334. PMID: 18790861, PMCID: PMC2576650, DOI: 10.1128/jb.00903-08.Peer-Reviewed Original ResearchMeSH KeywordsBacterial ProteinsBlotting, WesternElectrophoretic Mobility Shift AssayGene ExpressionGene Expression ProfilingGene Expression Regulation, BacterialIronIron DeficienciesOligonucleotide Array Sequence AnalysisOperonPromoter Regions, GeneticProtein BindingRepressor ProteinsReverse Transcriptase Polymerase Chain ReactionSalmonella entericaTranscription, GeneticConceptsFerrous iron transporter FeoBFur proteinIron-replete conditionsFur activityTarget genesIron-responsive genesWild-type levelsFerrous iron uptakeFeoAB operonFur geneTranscriptional activationIron acquisitionExpression experimentsRegulatory pathwaysTranscription levelsIron uptakeGenesPrimary regulatorRstAProteinFeOBRepressionSalmonella entericaPromoterExpressionOvercoming H-NS-mediated Transcriptional Silencing of Horizontally Acquired Genes by the PhoP and SlyA Proteins in Salmonella enterica *
Perez JC, Latifi T, Groisman EA. Overcoming H-NS-mediated Transcriptional Silencing of Horizontally Acquired Genes by the PhoP and SlyA Proteins in Salmonella enterica *. Journal Of Biological Chemistry 2008, 283: 10773-10783. PMID: 18270203, PMCID: PMC2447644, DOI: 10.1074/jbc.m709843200.Peer-Reviewed Original ResearchConceptsHistone-like nucleoid structuring proteinPagC geneSlyA proteinRNA polymeraseRNA polymerase recruitmentH-NS repressionNucleoid structuring proteinHorizontal gene transferDifferent regulatory proteinsSalmonella entericaPolymerase recruitmentTranscriptional silencingNew traitsForeign DNAGene transcriptionRegulatory proteinsUgtLRespective promotersTranscriptionPhoPRecipient organismGenesPagC promoterGene transferProtein
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
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 activationThe 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. coliPhoQ
2005
Analysis of differentially-regulated genes within a regulatory network by GPS genome navigation
Zwir I, Huang H, Groisman EA. Analysis of differentially-regulated genes within a regulatory network by GPS genome navigation. Bioinformatics 2005, 21: 4073-4083. PMID: 16159917, DOI: 10.1093/bioinformatics/bti672.Peer-Reviewed Original ResearchMeSH KeywordsAlgorithmsArtificial IntelligenceCluster AnalysisComputational BiologyDatabases, GeneticEscherichia coliEscherichia coli ProteinsGene Expression RegulationGene Expression Regulation, BacterialGenomeGenomicsPromoter Regions, GeneticResponse ElementsSalmonella entericaSoftwareTranscription, GeneticConceptsPhoP proteinRegulatory featuresGene expressionEnteric bacteria Escherichia coliCis-regulatory featuresCo-regulated promotersPost-genomic eraTranscription initiationRegulatory networksRegulatory interactionsGene transcriptionNovel memberExpression patternsBacteria Escherichia coliGenesEscherichia coliSalmonella entericaMultiple mechanismsProteinFundamental mechanismsExpressionRegulonTranscriptionPromoterReduced datasetThe 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 signalsPhoPGenesEffectorsProteinTranscriptional Regulation of the 4-Amino-4-deoxy-L-arabinose Biosynthetic Genes in Yersinia pestis *
Winfield MD, Latifi T, Groisman EA. Transcriptional Regulation of the 4-Amino-4-deoxy-L-arabinose Biosynthetic Genes in Yersinia pestis *. Journal Of Biological Chemistry 2005, 280: 14765-14772. PMID: 15710615, DOI: 10.1074/jbc.m413900200.Peer-Reviewed Original ResearchMeSH KeywordsAmino SugarsBacterial ProteinsBase SequenceBinding SitesCell ProliferationDeoxyribonuclease IDNA PrimersGene DeletionGene Expression Regulation, BacterialIronLipid AMagnesiumModels, BiologicalMolecular Sequence DataPlasmidsPolymyxin BPromoter Regions, GeneticSalmonella entericaSingle-Strand Specific DNA and RNA EndonucleasesTranscription FactorsTranscription, GeneticYersinia pestisConceptsPmrD proteinBiosynthetic genesPhoP/PhoQ systemTwo-component regulatory systemTranscription of PmrADisparate regulatory pathwaysYersinia pestisRelated bacterial speciesPmrA/PmrBSalmonella enterica serovar TyphimuriumPmrA proteinPhoP proteinGram-negative bacteriaTranscriptional regulationUgd geneMembrane remodelingEnterica serovar TyphimuriumRegulatory pathwaysCationic antimicrobial peptidesDistinct binding sitesBacterial membranesBacterial speciesDifferent promotersGenesPmrB proteinDissecting 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
Signal-dependent Binding of the Response Regulators PhoP and PmrA to Their Target Promoters in Vivo *
Shin D, Groisman EA. Signal-dependent Binding of the Response Regulators PhoP and PmrA to Their Target Promoters in Vivo *. Journal Of Biological Chemistry 2004, 280: 4089-4094. PMID: 15569664, DOI: 10.1074/jbc.m412741200.Peer-Reviewed Original ResearchConceptsResponse regulator PhoPPmrA proteinPhoP proteinRegulator PhoPTranscription of PhoPWild-type strainTarget promotersPromoter occupancyChromatin immunoprecipitationPromotes phosphorylationRegulatory regionsTarget genesPhoPValine residueLow Mg2GenesPhosphorylationPromoterProteinAsp 52TranscriptionSalmonella entericaVivoImmunoprecipitationMg2