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 Typhimurium
2022
Degradation 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 ResearchMeSH KeywordsAnimalsBacterial ProteinsDNA-Binding ProteinsEscherichia coliEscherichia coli ProteinsGene Expression Regulation, BacterialGene SilencingMammalsMiceProtease LaConceptsH-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 mechanismColonizationDifferential 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
Low 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 ResearchMeSH KeywordsAdenosine TriphosphateBacterial ProteinsBiological TransportCation Transport ProteinsCytoplasmGene Expression Regulation, BacterialHomeostasisMagnesiumMicrobial ViabilityMutationPhosphatesProtein BiosynthesisSalmonella typhimuriumConceptsCytoplasmic MgPhosphate assimilationRibosomal RNARegulatory logicP assimilationMolecular basisLoss of viabilityProtein inhibitsPi toxicityAdenosine triphosphateATP synthesisProtein synthesisATP accumulationHomeostasisBacterial growthCytosolic PiDependent processesMagnesium homeostasisBacteriaBiological moleculesInorganic orthophosphateEssential componentAssimilationGrowthRNA
2020
Horizontally 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 TyphimuriumVirulenceTranscriptionPromoterRegulatorFEDS: 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 ResearchMeSH KeywordsDNA, BacterialDNA, SuperhelicalEscherichia coliFluorescenceGene Expression Regulation, BacterialHigh-Throughput Screening AssaysPlasmidsSalmonella entericaTranscription, GeneticConceptsDNA 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 ResearchMeSH KeywordsBacterial ProteinsGene Expression Regulation, BacterialMultienzyme ComplexesPhosphorylationProtein KinasesProtein Processing, Post-TranslationalQuorum SensingSalmonella entericaSignal TransductionTrans-ActivatorsConceptsBarA/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
2018
Dietary sugar silences a colonization factor in a mammalian gut symbiont
Townsend GE, Han W, Schwalm ND, Raghavan V, Barry NA, Goodman AL, Groisman EA. Dietary sugar silences a colonization factor in a mammalian gut symbiont. Proceedings Of The National Academy Of Sciences Of The United States Of America 2018, 116: 233-238. PMID: 30559205, PMCID: PMC6320540, DOI: 10.1073/pnas.1813780115.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBacterial ProteinsBacteroides thetaiotaomicronDietary CarbohydratesDietary SugarsFructoseGastrointestinal MicrobiomeGene Expression Regulation, BacterialGene SilencingGlucoseMicePolysaccharidesSymbiosisA 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 ResearchMeSH KeywordsAdaptation, PhysiologicalAdenosine TriphosphateAnimalsBacterial ProteinsCell LineGene Expression Regulation, BacterialMacrophagesMiceMicrobial ViabilitySalmonella typhimuriumVirulenceVirulence FactorsConceptsVirulence 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 ResearchMeSH KeywordsAnti-Bacterial AgentsBacterial ProteinsCell MembraneDrug Resistance, BacterialGene Expression Regulation, BacterialKineticsLipid AMagnesiumPolymyxin BSalmonella typhimuriumConceptsLipid ALvr, 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 pathwayVirulence
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 activationNavigating the Gut Buffet: Control of Polysaccharide Utilization in Bacteroides spp.
Schwalm ND, Groisman EA. Navigating the Gut Buffet: Control of Polysaccharide Utilization in Bacteroides spp. Trends In Microbiology 2017, 25: 1005-1015. PMID: 28733133, DOI: 10.1016/j.tim.2017.06.009.Peer-Reviewed Original ResearchBacterial ProteinsBacteroidesGastrointestinal MicrobiomeGastrointestinal TractGene Expression Regulation, BacterialHumansPolysaccharidesSymbiosisSequestration 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 levelsGenesMgtCResiduesTranscriptionTerminusProteolysisProteinSubstrateProteaseBacteriaDegradationSequestrationATP-Dependent Persister Formation in Escherichia coli
Shan Y, Gandt A, Rowe S, Deisinger J, Conlon B, Lewis K, Zgurskaya H, Groisman E. ATP-Dependent Persister Formation in Escherichia coli. MBio 2017, 8: e02267-16. PMID: 28174313, PMCID: PMC5296605, DOI: 10.1128/mbio.02267-16.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine TriphosphateDrug ToleranceEscherichia coliGene Expression Regulation, BacterialMicrobial ViabilityConceptsChronic infectionFluorescence-activated cell sortingDrug toleranceATP levelsPersister formationDrug-tolerant persistersFluoroquinolone treatmentStress-induced activationSubpopulation of cellsLevels of ATPDormant variantsAntibiotic-tolerant cellsCellular ATP levelsBactericidal antibioticsDim cellsInfectionActivationPersister cellsAntibioticsCell sortingTreatmentSubpopulationsCellsActive toxinToxin activationPrioritization of polysaccharide utilization and control of regulator activation in Bacteroides thetaiotaomicron
Schwalm ND, Townsend GE, Groisman EA. Prioritization of polysaccharide utilization and control of regulator activation in Bacteroides thetaiotaomicron. Molecular Microbiology 2017, 104: 32-45. PMID: 28009067, DOI: 10.1111/mmi.13609.Peer-Reviewed Original ResearchMeSH KeywordsBacterial ProteinsBacteroidesBacteroides thetaiotaomicronDietary CarbohydratesGastrointestinal TractGene Expression Regulation, BacterialHumansPhosphorylationPolysaccharidesSymbiosisTranscriptional ActivationConceptsBacteroides thetaiotaomicronGut symbiotic bacteriumSites of phosphorylationB. thetaiotaomicronDiauxic growthTwo-component systemResponse regulatorSensor kinaseMyriad of hostPolysaccharide utilizationUnaltered growthSymbiotic bacteriumMammalian gutSingle polypeptideMultiple polysaccharidesSingle polysaccharidePhosphorylationSpecific signalsPresence of glucoseThetaiotaomicronTranscriptionGenesBacteriumArabinanPolysaccharides
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 Mg2TranslationProteinAbundanceMultiple 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