2023
Advancing evolution: Bacteria break down gene silencer to express horizontally acquired genes
Groisman E, Choi J. Advancing evolution: Bacteria break down gene silencer to express horizontally acquired genes. BioEssays 2023, 45: e2300062. PMID: 37533411, PMCID: PMC10530229, DOI: 10.1002/bies.202300062.Peer-Reviewed Original ResearchMeSH KeywordsBacteriaBacterial ProteinsDNA-Binding ProteinsDNA-Directed RNA PolymerasesGene Expression Regulation, BacterialSalmonella typhimuriumConceptsH-NSAT-rich DNAHeat-stable nucleoid-structuring (H-NS) proteinConserved amino acid sequencesNucleoid structuring proteinHorizontal gene transferAmino acid sequenceSalmonella enterica serovar TyphimuriumBacterial evolutionLon proteaseProtease LonDiverse bacteriaEnterica serovar TyphimuriumRNA polymeraseAlternative promotersAcid sequenceStructuring proteinGene silencersGenesCleavage siteEnteric bacteriaEscherichia coliGene transferCommensal Escherichia coliSerovar TyphimuriumHow Bacterial Pathogens Coordinate Appetite with Virulence
Pokorzynski N, Groisman E. How Bacterial Pathogens Coordinate Appetite with Virulence. Microbiology And Molecular Biology Reviews 2023, 87: e00198-22. PMID: 37358444, PMCID: PMC10521370, DOI: 10.1128/mmbr.00198-22.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAppetiteBacteriaBacterial ProteinsCarbonHumansMiceSalmonella typhimuriumVirulenceVirulence FactorsConceptsVirulence factorsTyphoid-like diseaseIntestinal inflammationFacultative intracellular pathogenImmunocompetent humansGut microbiotaPathogenic outcomesUtilization determinantsIntracellular pathogensSpecific nutrientsAntimicrobial agentsInfectionBacterial pathogensSerovar TyphimuriumBacterial virulencePathogensPathogenic traitsAnimal hostsPathwaySuch pathwaysCertain pathwaysMetabolic pathwaysVirulence programInflammationVirulence
2022
Differential synthesis of novel small protein times Salmonella virulence program
Salvail H, Choi J, Groisman EA. Differential synthesis of novel small protein times Salmonella virulence program. PLOS Genetics 2022, 18: e1010074. PMID: 35245279, PMCID: PMC8896665, DOI: 10.1371/journal.pgen.1010074.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBacterial ProteinsGene Expression Regulation, BacterialRNA, MessengerSalmonella typhimuriumVirulenceConceptsVirulence programPhoP/PhoQCold-blooded animalsSalmonella enterica serovar TyphimuriumAncestral regulatorGene organizationBicistronic operonEnterica serovar TyphimuriumPolycistronic mRNACellular processesGene controlCorresponding proteinMRNA speciesOperonPhoP phosphorylationGenesSerovar TyphimuriumDifferential synthesisPremature activationS. entericaMRNATranslationUgtLPhoQRibosomes
2021
RNA chaperone activates Salmonella virulence program during infection
Choi J, Salvail H, Groisman EA. RNA chaperone activates Salmonella virulence program during infection. Nucleic Acids Research 2021, 49: 11614-11628. PMID: 34751407, PMCID: PMC8599858, DOI: 10.1093/nar/gkab992.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBacterial ProteinsCell LineHeat-Shock ProteinsMacrophagesMembrane ProteinsMiceRNA StabilityRNA, MessengerSalmonella typhimuriumConceptsPhoP activationVirulence regulator PhoPWild-type virulenceBacterium Salmonella enterica serovar TyphimuriumWild-type S. typhimuriumSalmonella enterica serovar TyphimuriumRNA chaperonesEnterica serovar TyphimuriumRegulator PhoPRedundant proteinsMutant behavesVirulence programVirulence roleS. typhimuriumInside macrophagesSecondary structureSerovar TyphimuriumCritical functionsVirulence genesChaperonesPhoPMutantsRibosomesOrganismsCSPCHow 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 ResearchMeSH KeywordsBacterial ProteinsCytoplasmGene Expression Regulation, BacterialHeat-Shock ProteinsMagnesiumProtease LaSalmonella typhimuriumSubstrate SpecificityConceptsBacterium 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 ResearchMeSH KeywordsAdenosine TriphosphateATPases Associated with Diverse Cellular ActivitiesBacterial ProteinsCarbonMagnesiumNitrogenProteolysisSalmonella typhimuriumConceptsATP-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 ResearchMeSH KeywordsDNA GyraseDNA Topoisomerases, Type IDNA, SuperhelicalEscherichia coliMagnesiumPutrescineSalmonella typhimuriumSpermidineConceptsE. 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 activationHorizontally acquired regulatory gene activates ancestral regulatory system to promote Salmonella virulence
Choi J, Groisman EA. Horizontally acquired regulatory gene activates ancestral regulatory system to promote Salmonella virulence. Nucleic Acids Research 2020, 48: 10832-10847. PMID: 33045730, PMCID: PMC7641745, DOI: 10.1093/nar/gkaa813.Peer-Reviewed Original ResearchConceptsPhoP/PhoQAncestral regulatorNucleoid structuring protein H-NSProtein H-NSS. bongoriSalmonella enterica serovar TyphimuriumAncestral genomesH-NSTarget promotersEnterica serovar TyphimuriumRegulatory genesBacterial virulenceSalmonella virulencePromoter regionSsrBOpposite regulationGenesS. typhimuriumPhoQRegulatory systemSerovar TyphimuriumVirulenceTranscriptionPromoterRegulatorHow 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 ResearchMeSH KeywordsAnimalsCation Transport ProteinsHost-Pathogen InteractionsHumansMacrophagesMagnesiumSalmonella InfectionsSalmonella typhimuriumConceptsNutritional 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 ResearchMeSH KeywordsAnimalsBacterial ProteinsCation Transport ProteinsCell LineMacrophagesMagnesiumMicePlasmidsSalmonella typhimuriumVirulenceConceptsSmall proteinsAmino acid identityFacultative intracellular pathogenTransporter MgtAProtease FtsHMagnesium transportersAcid identityMacrophage proteinRelated transportersSame transcriptPathogen survivalMgtBIntracellular pathogensSerovar TyphimuriumProteinLimitation conditionsHost tissuesMgtROxidative stressTransportersSalmonella survivalSingular exampleFtsHMacrophagesMgtASalmonella 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
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 actionGene 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 ResearchConceptsLipid AProtein 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 activationSequestration 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 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