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
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 fluorescenceSalmonella expresses foreign genes during infection by degrading their silencer
Choi J, Groisman EA. Salmonella expresses foreign genes during infection by degrading their silencer. Proceedings Of The National Academy Of Sciences Of The United States Of America 2020, 117: 8074-8082. PMID: 32209674, PMCID: PMC7149492, DOI: 10.1073/pnas.1912808117.Peer-Reviewed Original ResearchConceptsForeign genesH-NSForeign DNAHeat-stable nucleoid-structuring (H-NS) proteinH-NS bindingNucleoid structuring proteinGram-negative bacterial speciesFacultative intracellular pathogenPhoP proteinLon proteaseProtease LonRegulatory sequencesVirulence regulatorGene silencingIntramacrophage survivalStructuring proteinBacterial speciesGenesInside macrophagesIntracellular pathogensSerovar TyphimuriumUncovered mechanismProteinVirulence genesDNA
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 pathwayVirulenceProtein synthesis controls phosphate homeostasis
Pontes MH, Groisman EA. Protein synthesis controls phosphate homeostasis. Genes & Development 2018, 32: 79-92. PMID: 29437726, PMCID: PMC5828397, DOI: 10.1101/gad.309245.117.Peer-Reviewed Original ResearchConceptsPi starvation responsesStarvation responseProtein synthesisPi transporter genesProtein synthesis controlATP consumptionPi starvationRegulatory connectionsPi homeostasisTransporter geneExtracellular milieuCytoplasmic MgCytoplasmic PiSerovar TyphimuriumPharmacological inhibitionATP levelsRibosomesCytoplasmic magnesiumBacteriumHomeostasisSynthesis controlPhoBSaccharomycesTranscriptionYeast
2017
Sequestration from Protease Adaptor Confers Differential Stability to Protease Substrate
Yeom J, Wayne KJ, Groisman EA. Sequestration from Protease Adaptor Confers Differential Stability to Protease Substrate. Molecular Cell 2017, 66: 234-246.e5. PMID: 28431231, PMCID: PMC5424706, DOI: 10.1016/j.molcel.2017.03.009.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceBacterial ProteinsBinding, CompetitiveCation Transport ProteinsEndopeptidase ClpGene Expression Regulation, BacterialHalf-LifeModels, MolecularMutationProtein BindingProtein Interaction Domains and MotifsProtein StabilityProteolysisSalmonella typhimuriumStructure-Activity RelationshipSubstrate SpecificityTime FactorsTranscription, GeneticConceptsN-terminal residuesSpecific N-terminal residuesRegulatory protein PhoPN-end ruleProtease ClpAPTemporal transcriptionMgtC geneN-terminusPhoPSpecific substratesClpAPDifferential stabilityProtein levelsGenesMgtCResiduesTranscriptionTerminusProteolysisProteinSubstrateProteaseBacteriaDegradationSequestration
2016
Multiple Signals Govern Utilization of a Polysaccharide in the Gut Bacterium Bacteroides thetaiotaomicron
Schwalm ND, Townsend GE, Groisman EA. Multiple Signals Govern Utilization of a Polysaccharide in the Gut Bacterium Bacteroides thetaiotaomicron. MBio 2016, 7: 10.1128/mbio.01342-16. PMID: 27729509, PMCID: PMC5061871, DOI: 10.1128/mbio.01342-16.Peer-Reviewed Original ResearchConceptsMammalian gut microbiotaPolysaccharide utilization genesUtilization genesHost dietGut symbiont Bacteroides thetaiotaomicronComplex polysaccharidesBacteroides thetaiotaomicronPleiotropic transcriptional regulatorDomains of lifeSubset of organismsRegulatory paradigmCritical nutrient sourceTranscriptional activatorTranscriptional regulatorsTranscriptional repressorCentral metabolismGenomic analysisMammalian gutMammalian hostsRegulatory architectureGut BacteroidesPolymeric fructanGut microbiotaGut bacteriumPolysaccharide breakdown
2015
An RNA motif advances transcription by preventing Rho-dependent termination
Sevostyanova A, Groisman EA. An RNA motif advances transcription by preventing Rho-dependent termination. Proceedings Of The National Academy Of Sciences Of The United States Of America 2015, 112: e6835-e6843. PMID: 26630006, PMCID: PMC4687561, DOI: 10.1073/pnas.1515383112.Peer-Reviewed Original ResearchConceptsRho-dependent transcription terminationTranscription terminationRNA elementsNucleic Acid Binding ProteinsRho-dependent terminationOpen reading frameRNA polymeraseReading frameBacterial RNALeader regionRNA motifsRNA conformationRho's accessInefficient translationBinding proteinInactive complexPharmacological inhibitionRhoTranscriptionWhen Too Much ATP Is Bad for Protein Synthesis
Pontes MH, Sevostyanova A, Groisman EA. When Too Much ATP Is Bad for Protein Synthesis. Journal Of Molecular Biology 2015, 427: 2586-2594. PMID: 26150063, PMCID: PMC4531837, DOI: 10.1016/j.jmb.2015.06.021.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine TriphosphateEnergy MetabolismEscherichia coliHumansMagnesiumProtein BiosynthesisRibosomesTranscription, GeneticConceptsProtein synthesisStructure of ribosomesEnergy-dependent activitiesATP levelsRibosome productionCellular processesTranslation initiationCytoplasmic membraneEssential enzymeCellular ATPEnergy currencyLiving cellsATPCellsDivalent cationsCrucial roleTriphosphateRibosomesAminoacylationOrganismsNon-physiological increaseCofactorEnzymeBiochemistryCommon divalent cations
2014
Bacterial Nucleoid-Associated Protein Uncouples Transcription Levels from Transcription Timing
Zwir I, Yeo WS, Shin D, Latifi T, Huang H, Groisman EA. Bacterial Nucleoid-Associated Protein Uncouples Transcription Levels from Transcription Timing. MBio 2014, 5: 10.1128/mbio.01485-14. PMID: 25293763, PMCID: PMC4196223, DOI: 10.1128/mbio.01485-14.Peer-Reviewed Original ResearchMeSH KeywordsBacterial ProteinsDNA-Binding ProteinsGene Expression Regulation, BacterialSalmonella typhimuriumTime FactorsTranscription, GeneticConceptsTranscription timingPhoP proteinAncestral geneExpression timingTranscriptional regulatorsGene ancestryTranscription factorsTranscription levelsHistone-like nucleoid structuring proteinHigher mRNA levelsExpression behaviorH-NS proteinNucleoid structuring proteinBacterium Salmonella enterica serovar TyphimuriumExpression of genesSalmonella enterica serovar TyphimuriumH-NSLatter genesEnterica serovar TyphimuriumMRNA levelsCorresponding promotersTarget genesDevelopmental pathwaysEarly genesGenesTuning transcription of nutrient utilization genes to catabolic rate promotes growth in a gut bacterium
Raghavan V, Lowe EC, Townsend GE, Bolam DN, Groisman EA. Tuning transcription of nutrient utilization genes to catabolic rate promotes growth in a gut bacterium. Molecular Microbiology 2014, 93: 1010-1025. PMID: 25041429, DOI: 10.1111/mmi.12714.Peer-Reviewed Original ResearchMeSH KeywordsBacterial ProteinsBacteroidesChondroitin SulfatesGastrointestinal TractHumansTranscription, GeneticConceptsUtilization genesRate-determining enzymeGut symbiont Bacteroides thetaiotaomicronB. thetaiotaomicronExcess chondroitin sulfateCatabolic genesChondroitin sulfateNutrient availabilityConstitutive expressionBacteroides thetaiotaomicronGenesGut environmentCatabolic rateTranscriptionTransient increaseThetaiotaomicronAnalogous mechanismEnzymeRegulatorExposureTranscripts
2012
The promoter architectural landscape of the Salmonella PhoP regulon
Zwir I, Latifi T, Perez JC, Huang H, Groisman EA. The promoter architectural landscape of the Salmonella PhoP regulon. Molecular Microbiology 2012, 84: 463-485. PMID: 22435712, PMCID: PMC3335776, DOI: 10.1111/j.1365-2958.2012.08036.x.Peer-Reviewed Original ResearchConceptsPromoter architectureDistinct promoter architecturesPathogen Salmonella enterica serovar TyphimuriumGene expression behaviorSalmonella enterica serovar TyphimuriumEnterica serovar TyphimuriumPhoP regulonPromoter featuresBiochemical functionsPhoPExpression behaviorPhysiological roleBacterial activatorsGenesSerovar TyphimuriumPromoterRegulonDifferent mechanismsTranscriptionVirulenceActivatorAncestryExpressionLarge numberLimited numberRiboswitch control of Rho-dependent transcription termination
Hollands K, Proshkin S, Sklyarova S, Epshtein V, Mironov A, Nudler E, Groisman EA. Riboswitch control of Rho-dependent transcription termination. Proceedings Of The National Academy Of Sciences Of The United States Of America 2012, 109: 5376-5381. PMID: 22431636, PMCID: PMC3325659, DOI: 10.1073/pnas.1112211109.Peer-Reviewed Original ResearchMeSH KeywordsBase SequenceMolecular Sequence DataNucleic Acid ConformationRho GTP-Binding ProteinsRiboswitchTerminator Regions, GeneticTranscription, GeneticConceptsRho-dependent transcription terminationTranscription terminationRiboswitch ligandsGene expressionControl gene expressionRho-specific inhibitorIntrinsic transcription terminationATPase activityActivity of RhoSalmonella enterica serovar TyphimuriumRiboswitch actionRiboswitch controlTranscription machineryProtein effectorsGene regulationRho ATPase activityEnterica serovar TyphimuriumTranslation initiationThird general mechanismRiboswitchTranscriptionEscherichia coliRNA sensorsWidespread modeSerovar Typhimurium
2011
Genome-wide detection of novel regulatory RNAs in E. coli
Raghavan R, Groisman EA, Ochman H. Genome-wide detection of novel regulatory RNAs in E. coli. Genome Research 2011, 21: 1487-1497. PMID: 21665928, PMCID: PMC3166833, DOI: 10.1101/gr.119370.110.Peer-Reviewed Original ResearchConceptsSmall RNAsLeader sequenceIntergenic regionRegulatory elementsRegulatory RNAsNew small RNAsStable RNA secondary structureNovel regulatory RNAsProtein-coding transcriptsNovel small RNAsGenome-wide detectionNoncoding regulatory RNAsE. coliRNA secondary structureProtein HfqPhylogenetic conservationBacterial genomesEvolutionary analysisPresence of hundredsSequencing approachGene expressionCompensatory mutationsEnteric speciesSecondary structureEscherichia coli
2010
A Bacterial mRNA Leader that Employs Different Mechanisms to Sense Disparate Intracellular Signals
Park SY, Cromie MJ, Lee EJ, Groisman EA. A Bacterial mRNA Leader that Employs Different Mechanisms to Sense Disparate Intracellular Signals. Cell 2010, 142: 737-748. PMID: 20813261, PMCID: PMC2967377, DOI: 10.1016/j.cell.2010.07.046.Peer-Reviewed Original ResearchMeSH Keywords5' Untranslated RegionsAdenosine TriphosphatasesBacterial ProteinsBase SequenceGene Expression Regulation, BacterialMagnesiumMembrane Transport ProteinsMolecular Sequence DataProlineRegulatory Sequences, Ribonucleic AcidRNA, MessengerSalmonella typhimuriumSequence AlignmentTranscription, GeneticConceptsLeader sequencePositive 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
2008
Evolution and Dynamics of Regulatory Architectures Controlling Polymyxin B Resistance in Enteric Bacteria
Mitrophanov AY, Jewett MW, Hadley TJ, Groisman EA. Evolution and Dynamics of Regulatory Architectures Controlling Polymyxin B Resistance in Enteric Bacteria. PLOS Genetics 2008, 4: e1000233. PMID: 18949034, PMCID: PMC2565834, DOI: 10.1371/journal.pgen.1000233.Peer-Reviewed Original ResearchConceptsRegulatory architectureComplex genetic networksDirect transcriptional controlEnteric bacteriaPolymyxin B resistanceEvolutionary historyTranscriptional controlGenetic networksRegulatory proteinsRegulatory pathwaysCellular responsesStructural modulesIndirect regulationRapid activationB resistanceExpression levelsMRNA expression levelsAntibiotic polymyxin BRegulation circuitBacteriaInducible resistanceFunctional propertiesProteinSystem postTransitional stageRstA-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 transferProteinThe 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 ResearchMeSH KeywordsBacterial ProteinsGenes, BacterialMetabolic Networks and PathwaysModels, BiologicalRegulonSalmonella typhimuriumSignal TransductionTranscription, GeneticVirulenceConceptsTwo-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