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 ResearchConceptsH-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 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 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 ResearchConceptsVirulence programPhoP/PhoQCold-blooded animalsSalmonella enterica serovar TyphimuriumAncestral regulatorGene organizationBicistronic operonEnterica serovar TyphimuriumPolycistronic mRNACellular processesGene controlCorresponding proteinMRNA speciesOperonPhoP phosphorylationGenesSerovar TyphimuriumDifferential synthesisPremature activationS. entericaMRNATranslationUgtLPhoQRibosomes
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 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 fluorescenceA Physiological Basis for Nonheritable Antibiotic Resistance
Pontes MH, Groisman EA. A Physiological Basis for Nonheritable Antibiotic Resistance. MBio 2020, 11: 10.1128/mbio.00817-20. PMID: 32546621, PMCID: PMC7298711, DOI: 10.1128/mbio.00817-20.Peer-Reviewed Original ResearchConceptsNonheritable resistanceAntibiotic toleranceCore cellular processesAcquisition of genesToxin-antitoxin modulesExpression of genesSlow bacterial growthActivity of toxinsAbility of bacteriaBacterial genomesCellular processesNutrient limitationBacterial growthGuanosine tetraphosphateGenetic changesBacterial populationsFeedback inhibitionPhysiological basisGenesOrganismsSmall subpopulationBacteriostatic antibioticsAntibiotic resistanceGenomeToleranceThe 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 genesDNAA Master Regulator of Bacteroides thetaiotaomicron Gut Colonization Controls Carbohydrate Utilization and an Alternative Protein Synthesis Factor
Townsend GE, Han W, Schwalm ND, Hong X, Bencivenga-Barry NA, Goodman AL, Groisman EA. A Master Regulator of Bacteroides thetaiotaomicron Gut Colonization Controls Carbohydrate Utilization and an Alternative Protein Synthesis Factor. MBio 2020, 11: 10.1128/mbio.03221-19. PMID: 31992627, PMCID: PMC6989115, DOI: 10.1128/mbio.03221-19.Peer-Reviewed Original ResearchPutative translation factorProtein synthesis factorsTranslation factorsMammalian gutDietary fiber utilizationTranscriptional regulatorsBeneficial microbesSpecialized translation factorHundreds of genesMajor transcriptional regulatorGut colonizationCarbohydrate utilizationSynthesis factorsHuman gut microbiotaGlobal regulonGenetic repertoireTranscription factorsMaster regulatorDNA sequencesDerive nutrientsColonization defectUtilization of carbohydratesCellular metabolismComplex polysaccharidesGenes
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 conditionsGenesAdaptorAbundanceUnfoldaseFtsATranscriptionSubunitsSubstrateProteolysisVirulenceProteinBindsLvr, 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
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 levelsGenesMgtCResiduesTranscriptionTerminusProteolysisProteinSubstrateProteaseBacteriaDegradationSequestrationPrioritization 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 ResearchConceptsBacteroides 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 Mg2TranslationProteinAbundance
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 TyphimuriumGenesRhoSpecies-Specific Dynamic Responses of Gut Bacteria to a Mammalian Glycan
Raghavan V, Groisman EA. Species-Specific Dynamic Responses of Gut Bacteria to a Mammalian Glycan. Journal Of Bacteriology 2015, 197: 1538-1548. PMID: 25691527, PMCID: PMC4403648, DOI: 10.1128/jb.00010-15.Peer-Reviewed Original ResearchConceptsUtilization genesRelated speciesBacterial speciesBacteroides speciesPolysaccharide utilization genesCase of genesGut bacteriaGut bacterial speciesOrthologous genesCommunity compositionExpression dynamicsMammalian glycansSole carbon sourceRelated microbesBacterial communitiesMicrobial speciesMammalian intestineSame geneStable coexistenceGut microbial compositionDifferential regulationExpression behaviorGenesMicrobial compositionSustained activationFlagella-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
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 ResearchConceptsTranscription 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 ResearchConceptsUtilization genesRate-determining enzymeGut symbiont Bacteroides thetaiotaomicronB. thetaiotaomicronExcess chondroitin sulfateCatabolic genesChondroitin sulfateNutrient availabilityConstitutive expressionBacteroides thetaiotaomicronGenesGut environmentCatabolic rateTranscriptionTransient increaseThetaiotaomicronAnalogous mechanismEnzymeRegulatorExposureTranscripts