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
2022
Gut colonization by Bacteroides requires translation by an EF‐G paralog lacking GTPase activity
Han W, Peng B, Wang C, Townsend G, Barry N, Peske F, Goodman A, Liu J, Rodnina M, Groisman E. Gut colonization by Bacteroides requires translation by an EF‐G paralog lacking GTPase activity. The EMBO Journal 2022, 42: embj2022112372. PMID: 36472247, PMCID: PMC9841332, DOI: 10.15252/embj.2022112372.Peer-Reviewed Original ResearchConceptsEF-G1Protein synthesisGTPase activityGuanosine triphosphateElongation factor GCarbon starvationCellular processesStarvation conditionsBacteroides thetaiotaomicronFactor GSingular abilityAmino acidsCell growthParalogsMurine cecumTranslocationGut colonizationColonizationCellsRibosomesProteinStarvationThetaiotaomicronBacteriaFitnessDegradation of gene silencer is essential for expression of foreign genes and bacterial colonization of the mammalian gut
Choi J, Schmukler M, Groisman EA. Degradation of gene silencer is essential for expression of foreign genes and bacterial colonization of the mammalian gut. Proceedings Of The National Academy Of Sciences Of The United States Of America 2022, 119: e2210239119. PMID: 36161931, PMCID: PMC9546599, DOI: 10.1073/pnas.2210239119.Peer-Reviewed Original ResearchConceptsH-NSForeign genesHeat-stable nucleoid-structuring (H-NS) proteinWild-type H-NSNucleoid-associated proteinsH-NS proteinsNucleoid structuring proteinHorizontal gene transferBacterial evolutionLon proteaseSilences expressionCorresponding genesForeign DNAMammalian gutMammalian hostsStructuring proteinGene silencersGenesMurine gutEnteric bacteriaGene transferBiofilm formationProteinGeneral mechanismColonization
2021
Cellular Adaptations to Cytoplasmic Mg2+ Limitation
Groisman EA, Chan C. Cellular Adaptations to Cytoplasmic Mg2+ Limitation. Annual Review Of Microbiology 2021, 75: 649-672. PMID: 34623895, DOI: 10.1146/annurev-micro-020518-115606.Peer-Reviewed Original ResearchConceptsCytoplasmic MgLeader regionATP-dependent proteaseTranscriptional regulator PhoPAbundant divalent cationOpen reading frameActivity of ribosomesSimilar adaptation strategiesRegulated proteolysisExpression of proteinsRegulator PhoPMicrobial speciesReading frameCellular adaptationDifferent genesCoding regionsBacterial speciesProtein synthesisSpeciesProteinAbundanceDivalent cationsExpressionCytoplasmic Mg2Enzymatic reactionsReduced 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
How 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 exampleFtsHMacrophagesMgtAFEDS: 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 entericaGenesSalmonella 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
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
2018
A protein that controls the onset of a Salmonella virulence program
Yeom J, Pontes MH, Choi J, Groisman EA. A protein that controls the onset of a Salmonella virulence program. The EMBO Journal 2018, 37: embj201796977. PMID: 29858228, PMCID: PMC6043847, DOI: 10.15252/embj.201796977.Peer-Reviewed Original ResearchConceptsVirulence programBacterial inner membraneMaster virulence regulatorC-terminal domainHost tissuesAnti-virulence factorMgtC proteinInner membraneGenetic programVirulence regulatorConstitutive promoterGene transcriptionIntramacrophage survivalSame mRNAAntibiotic toleranceATP synthesisPathogen survivalGenesMetabolic adaptationCytoplasmic pHSerovar TyphimuriumPathogen persistenceVirulence genesProteinMechanism of actionReduction in adaptor amounts establishes degradation hierarchy among protease substrates
Yeom J, Gao X, Groisman EA. Reduction in adaptor amounts establishes degradation hierarchy among protease substrates. Proceedings Of The National Academy Of Sciences Of The United States Of America 2018, 115: e4483-e4492. PMID: 29686082, PMCID: PMC5948988, DOI: 10.1073/pnas.1722246115.Peer-Reviewed Original ResearchConceptsRegulatory protein PhoPATP-dependent proteaseCritical cellular processesExpression of genesCellular processesAntibiotic persistersCytoplasmic MgProtease substratesUvrYDifferential stabilityProteasePhoPPhysiological conditionsGenesAdaptorAbundanceUnfoldaseFtsATranscriptionSubunitsSubstrateProteolysisVirulenceProteinBinds
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
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 Mg2TranslationProteinAbundance
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.TranscriptionCytoplasmicProteinThe lipopolysaccharide modification regulator PmrA limits Salmonella virulence by repressing the type three-secretion system Spi/Ssa
Choi J, Groisman EA. The lipopolysaccharide modification regulator PmrA limits Salmonella virulence by repressing the type three-secretion system Spi/Ssa. Proceedings Of The National Academy Of Sciences Of The United States Of America 2013, 110: 9499-9504. PMID: 23690578, PMCID: PMC3677452, DOI: 10.1073/pnas.1303420110.Peer-Reviewed Original ResearchConceptsPmrA proteinNull mutantsSalmonella virulenceThree secretion systemVirulence regulatory genesSalmonella enterica serovar TyphimuriumWild-type SalmonellaEnterica serovar TyphimuriumPmrA mutantRegulatory genesProtein bindsModification genesMurine typhoid feverControl expressionLPS modificationsPmrA geneMutantsGenesSerovar TyphimuriumPathogen persistenceAntimicrobial peptidesHost tissuesPromoterVirulenceProtein
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. entericaProtein