2024
Chaperone Hsp70 helps Salmonella survive infection-relevant stress by reducing protein synthesis
Chan C, Groisman E. Chaperone Hsp70 helps Salmonella survive infection-relevant stress by reducing protein synthesis. PLOS Biology 2024, 22: e3002560. PMID: 38574172, PMCID: PMC10994381, DOI: 10.1371/journal.pbio.3002560.Peer-Reviewed Original ResearchConceptsRibosome associationProtein synthesisProtein homeostasisS. typhimuriumProtein folding capacityPreventing protein aggregationC-terminal amino acidsDomains of lifeProtein synthesis in vitroInhibit protein synthesisFolding capacityHsp70 chaperonesJ-domainSynthesis in vitroProtein foldingReduction of protein synthesisChaperone Hsp70DnaKRibosomeProtein aggregationChaperoneAmino acidsProteinStarvationHSP70
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 formPhoPLow Cytoplasmic Magnesium Increases the Specificity of the Lon and ClpAP Proteases
Yeom J, Groisman EA. Low Cytoplasmic Magnesium Increases the Specificity of the Lon and ClpAP Proteases. Journal Of Bacteriology 2021, 203: 10.1128/jb.00143-21. PMID: 33941609, PMCID: PMC8223949, DOI: 10.1128/jb.00143-21.Peer-Reviewed Original ResearchConceptsBacterium Salmonella enterica serovar TyphimuriumCytoplasmic MgSalmonella enterica serovar TyphimuriumLon substratesClpAP proteaseEnterica serovar TyphimuriumAntibiotic persistenceEnteric bacteriaSerovar TyphimuriumSpectrum of substratesPhoP proteinProtease LonAcetyl coenzyme ATranscriptional regulatorsProtein bindsPhoP boxRegulatory proteinsProtease specificityPromoter regionCritical regulatorProtein synthesisLiving cellsLonPhoPEscherichia coliLimitation of phosphate assimilation maintains cytoplasmic magnesium homeostasis
Bruna RE, Kendra CG, Groisman EA, Pontes MH. Limitation of phosphate assimilation maintains cytoplasmic magnesium homeostasis. Proceedings Of The National Academy Of Sciences Of The United States Of America 2021, 118: e2021370118. PMID: 33707210, PMCID: PMC7980370, DOI: 10.1073/pnas.2021370118.Peer-Reviewed Original ResearchConceptsCytoplasmic MgPhosphate assimilationRibosomal RNARegulatory logicP assimilationMolecular basisLoss of viabilityProtein inhibitsPi toxicityAdenosine triphosphateATP synthesisProtein synthesisATP accumulationHomeostasisBacterial growthCytosolic PiDependent processesMagnesium homeostasisBacteriaBiological moleculesInorganic orthophosphateEssential componentAssimilationGrowthRNAReduced ATP-dependent proteolysis of functional proteins during nutrient limitation speeds the return of microbes to a growth state
Yeom J, Groisman EA. Reduced ATP-dependent proteolysis of functional proteins during nutrient limitation speeds the return of microbes to a growth state. Science Signaling 2021, 14 PMID: 33500334, PMCID: PMC8378506, DOI: 10.1126/scisignal.abc4235.Peer-Reviewed Original ResearchConceptsATP-dependent proteolysisSlow-growth stateFunctional proteinsGrowth stateATP-dependent proteaseTranscriptional regulator PhoPProtein preservationNutrient limitation conditionsRapid growth statesRegulator PhoPMicrobial strategiesNonfunctional proteinNutrient limitationProtein degradationNitrogen conditionsSame proteaseMagnesium starvationSerovar TyphimuriumProteinLimitation conditionsProteolysisIntracellular ATPParticular nutrientsStationary phaseIntracellular concentration
2020
DNA supercoiling differences in bacteria result from disparate DNA gyrase activation by polyamines
Duprey A, Groisman EA. DNA supercoiling differences in bacteria result from disparate DNA gyrase activation by polyamines. PLOS Genetics 2020, 16: e1009085. PMID: 33125364, PMCID: PMC7598504, DOI: 10.1371/journal.pgen.1009085.Peer-Reviewed Original ResearchConceptsE. coli enzymeDNA supercoilingColi enzymeDNA supercoiling resultsGlobal DNA supercoilingDNA gyraseSignal transduction pathwaysAmino acid identityDNA gyrase activityE. coliSpecies Escherichia coliSalmonella enterica serovar TyphimuriumEnterica serovar TyphimuriumAcid identityTransduction pathwaysPrecursor putrescineGyrase activitySupercoilingHigh extracellular Mg2DNA gyrasesPolyamines spermidineEscherichia coliTopoisomerase ISerovar TyphimuriumDisparate activationHow Pathogens Feel and Overcome Magnesium Limitation When in Host Tissues
Blanc-Potard AB, Groisman EA. How Pathogens Feel and Overcome Magnesium Limitation When in Host Tissues. Trends In Microbiology 2020, 29: 98-106. PMID: 32807623, PMCID: PMC7855738, DOI: 10.1016/j.tim.2020.07.003.Peer-Reviewed Original ResearchConceptsNutritional immunityHost cell compartmentsAbundant divalent cationHost tissuesSalmonella enterica serovar TyphimuriumAvailability of nutrientsPathogen responseEnterica serovar TyphimuriumMacrophage proteinHost organismLiving cellsMagnesium limitationAmino acidsIntracellular pathogensSerovar TyphimuriumNutrient concentrationsCell compartmentPathogensDivalent cationsNutrientsMagnesium deprivationEssentialityOrganismsCytoplasmProteinSmall proteins regulate Salmonella survival inside macrophages by controlling degradation of a magnesium transporter
Yeom J, Shao Y, Groisman EA. Small proteins regulate Salmonella survival inside macrophages by controlling degradation of a magnesium transporter. Proceedings Of The National Academy Of Sciences Of The United States Of America 2020, 117: 20235-20243. PMID: 32753384, PMCID: PMC7443967, DOI: 10.1073/pnas.2006116117.Peer-Reviewed Original ResearchConceptsSmall proteinsAmino acid identityFacultative intracellular pathogenTransporter MgtAProtease FtsHMagnesium transportersAcid identityMacrophage proteinRelated transportersSame transcriptPathogen survivalMgtBIntracellular pathogensSerovar TyphimuriumProteinLimitation conditionsHost tissuesMgtROxidative stressTransportersSalmonella survivalSingular exampleFtsHMacrophagesMgtA
2018
Gene expression kinetics governs stimulus-specific decoration of the Salmonella outer membrane
Hong X, Chen HD, Groisman EA. Gene expression kinetics governs stimulus-specific decoration of the Salmonella outer membrane. Science Signaling 2018, 11 PMID: 29739882, PMCID: PMC5967240, DOI: 10.1126/scisignal.aar7921.Peer-Reviewed Original ResearchProtein 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
Activation of master virulence regulator PhoP in acidic pH requires the Salmonella-specific protein UgtL
Choi J, Groisman EA. Activation of master virulence regulator PhoP in acidic pH requires the Salmonella-specific protein UgtL. Science Signaling 2017, 10 PMID: 28851823, PMCID: PMC5966036, DOI: 10.1126/scisignal.aan6284.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntimicrobial Cationic PeptidesBacterial ProteinsDisease Models, AnimalFemaleGene Expression Regulation, BacterialHydrogen-Ion ConcentrationMagnesiumMembrane ProteinsMiceMice, Inbred BALB CPeptidesPhosphorylationSalmonella InfectionsSalmonella typhimuriumSignal TransductionVirulenceConceptsPhoP activation
2016
Reducing Ribosome Biosynthesis Promotes Translation during Low Mg2+ Stress
Pontes MH, Yeom J, Groisman EA. Reducing Ribosome Biosynthesis Promotes Translation during Low Mg2+ Stress. Molecular Cell 2016, 64: 480-492. PMID: 27746019, PMCID: PMC5500012, DOI: 10.1016/j.molcel.2016.05.008.Peer-Reviewed Original ResearchConceptsSynthesis of ribosomesAmino acid abundanceExpression of proteinsPromotes TranslationAvailability of ATPRibosomal componentsRegulatory circuitsTranslational arrestCytosolic MgRRNA geneProtein synthesisRibosomesATP levelsLevels of ATPATP amountATPDivalent cationsMutantsTranscriptionNegative chargeGenesLow Mg2TranslationProteinAbundanceAcidic pH sensing in the bacterial cytoplasm is required for Salmonella virulence
Choi J, Groisman EA. Acidic pH sensing in the bacterial cytoplasm is required for Salmonella virulence. Molecular Microbiology 2016, 101: 1024-1038. PMID: 27282333, PMCID: PMC5015592, DOI: 10.1111/mmi.13439.Peer-Reviewed Original Research
2015
The Bacterial Transcription Termination Factor Rho Coordinates Mg2+ Homeostasis with Translational Signals
Kriner MA, Groisman EA. The Bacterial Transcription Termination Factor Rho Coordinates Mg2+ Homeostasis with Translational Signals. Journal Of Molecular Biology 2015, 427: 3834-3849. PMID: 26523680, PMCID: PMC4964609, DOI: 10.1016/j.jmb.2015.10.020.Peer-Reviewed Original ResearchMeSH Keywords5' Untranslated RegionsAmino Acid SequenceBacterial ProteinsBase SequenceCation Transport ProteinsGene Expression Regulation, BacterialHomeostasisInverted Repeat SequencesMagnesiumMolecular Sequence DataNucleic Acid ConformationProtein BiosynthesisRho FactorSalmonella typhimuriumTranscription Initiation SiteConceptsLeader regionTranslational signalsGenome-wide activityShort open reading framesRho utilization siteRho-dependent terminationRho-dependent terminatorsOpen reading frameSalmonella enterica serovar TyphimuriumNascent RNATranscription terminationEnterica serovar TyphimuriumTransport genesProtein RhoRNA polymeraseReading frameLeader mRNASpecific genesRNA conformationEfficient translationExclusive conformationsTranscriptionSerovar TyphimuriumGenesRhoWhen 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 ResearchConceptsProtein synthesisStructure of ribosomesEnergy-dependent activitiesATP levelsRibosome productionCellular processesTranslation initiationCytoplasmic membraneEssential enzymeCellular ATPEnergy currencyLiving cellsATPCellsDivalent cationsCrucial roleTriphosphateRibosomesAminoacylationOrganismsNon-physiological increaseCofactorEnzymeBiochemistryCommon divalent cationsSalmonella promotes virulence by repressing cellulose production
Pontes MH, Lee EJ, Choi J, Groisman EA. Salmonella promotes virulence by repressing cellulose production. Proceedings Of The National Academy Of Sciences Of The United States Of America 2015, 112: 5183-5188. PMID: 25848006, PMCID: PMC4413311, DOI: 10.1073/pnas.1500989112.Peer-Reviewed Original ResearchConceptsCellulose synthesisWild-type phenotypeWild-type virulenceSalmonella enterica serovar TyphimuriumCyclic diguanylateEnterica serovar TyphimuriumPathogen fitnessAbundant organic polymerMgtC geneAcute virulenceAllosteric activatorAbiotic surfacesMgtC mutantInside macrophagesMutantsVirulence determinantsSerovar TyphimuriumVirulenceCellulose productionEnvironmental insultsCellulose levelsBCSAAttenuated mutantsTraitsDiguanylateFlagella-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
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
2013
Signal‐specific temporal response by the Salmonella PhoP/PhoQ regulatory system
Park S, Groisman EA. Signal‐specific temporal response by the Salmonella PhoP/PhoQ regulatory system. Molecular Microbiology 2013, 91: 135-144. PMID: 24256574, PMCID: PMC3890429, DOI: 10.1111/mmi.12449.Peer-Reviewed Original ResearchConceptsTransporter MgtATwo-component systems PhoP/PhoQPhoP-dependent genesAntimicrobial peptide C18G.PhoP/PhoQSalmonella enterica serovar TyphimuriumSensor PhoQEnterica serovar TyphimuriumVirulence functionsRepressing signalsGene setsPhoQMgtAGenesSerovar TyphimuriumElicit expressionPeriplasmPhoPActive formFull transcriptionExpressionPhoQ.TranscriptionCytoplasmicProteinBacterial Mg2+ Homeostasis, Transport, and Virulence
Groisman EA, Hollands K, Kriner MA, Lee EJ, Park SY, Pontes MH. Bacterial Mg2+ Homeostasis, Transport, and Virulence. Annual Review Of Genetics 2013, 47: 625-646. PMID: 24079267, PMCID: PMC4059682, DOI: 10.1146/annurev-genet-051313-051025.Peer-Reviewed Original Research