2023
Advancing the fitness of gut commensal bacteria
Groisman E, Han W, Krypotou E. Advancing the fitness of gut commensal bacteria. Science 2023, 382: 766-768. PMID: 37972163, PMCID: PMC10838159, DOI: 10.1126/science.adh9165.Peer-Reviewed Original ResearchHow 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 ResearchConceptsVirulence factorsTyphoid-like diseaseIntestinal inflammationFacultative intracellular pathogenImmunocompetent humansGut microbiotaPathogenic outcomesUtilization determinantsIntracellular pathogensSpecific nutrientsAntimicrobial agentsInfectionBacterial pathogensSerovar TyphimuriumBacterial virulencePathogensPathogenic traitsAnimal hostsPathwaySuch pathwaysCertain pathwaysMetabolic pathwaysVirulence programInflammationVirulenceBacteria require phase separation for fitness in the mammalian gut
Krypotou E, Townsend G, Gao X, Tachiyama S, Liu J, Pokorzynski N, Goodman A, Groisman E. Bacteria require phase separation for fitness in the mammalian gut. Science 2023, 379: 1149-1156. PMID: 36927025, PMCID: PMC10148683, DOI: 10.1126/science.abn7229.Peer-Reviewed Original ResearchConceptsMammalian gutTranscription termination factor RhoTermination factor RhoGene regulationTranscription terminationMechanisms bacteriaBacteria interactionsHuman commensalValuable targetBacteriaRhoGut microbiotaFitnessNovel clinical applicationsTherapeutic manipulationGutHuman healthCommensalRegulation
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
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 ResearchConceptsPhoP 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 genesChaperonesPhoPMutantsRibosomesOrganismsCSPC
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 TyphimuriumVirulenceTranscriptionPromoterRegulatorSmall 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 exampleFtsHMacrophagesMgtAA 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 resistanceGenomeToleranceSalmonella 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 ResearchA 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 action
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
2015
Salmonella 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 mutantsTraitsDiguanylate
2014
Control of a Salmonella virulence operon by proline-charged tRNAPro
Lee EJ, Choi J, Groisman EA. Control of a Salmonella virulence operon by proline-charged tRNAPro. Proceedings Of The National Academy Of Sciences Of The United States Of America 2014, 111: 3140-3145. PMID: 24516160, PMCID: PMC3939920, DOI: 10.1073/pnas.1316209111.Peer-Reviewed Original Research5' Untranslated RegionsAmino Acid SequenceAnimalsBacterial ProteinsBase PairingBase SequenceCation Transport ProteinsCodonGene Expression Regulation, BacterialHost-Pathogen InteractionsMiceMolecular Sequence DataOligodeoxyribonucleotidesOpen Reading FramesProlineReal-Time Polymerase Chain ReactionRNA, Transfer, ProSalmonella typhimuriumVirulence
2013
A Bacterial Virulence Protein Promotes Pathogenicity by Inhibiting the Bacterium’s Own F1Fo ATP Synthase
Lee EJ, Pontes MH, Groisman EA. A Bacterial Virulence Protein Promotes Pathogenicity by Inhibiting the Bacterium’s Own F1Fo ATP Synthase. Cell 2013, 154: 146-156. PMID: 23827679, PMCID: PMC3736803, DOI: 10.1016/j.cell.2013.06.004.Peer-Reviewed Original ResearchThe 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
Expression of STM4467-Encoded Arginine Deiminase Controlled by the STM4463 Regulator Contributes to Salmonella enterica Serovar Typhimurium Virulence
Choi Y, Choi J, Groisman EA, Kang DH, Shin D, Ryu S. Expression of STM4467-Encoded Arginine Deiminase Controlled by the STM4463 Regulator Contributes to Salmonella enterica Serovar Typhimurium Virulence. Infection And Immunity 2012, 80: 4291-4297. PMID: 23006851, PMCID: PMC3497419, DOI: 10.1128/iai.00880-12.Peer-Reviewed Original ResearchConceptsCarbamate kinaseOrnithine transcarbamoylaseArginine deiminaseSalmonella enterica Serovar Typhimurium VirulenceBacterium Salmonella enterica serovar TyphimuriumSalmonella enterica serovar TyphimuriumGene functionEnterica serovar TyphimuriumDeletion mutantsMammalian hostsPathway genesRegulatory proteinsADI systemSuccessful infectionTyphimurium virulenceS. typhimuriumMetabolic functionsGenesSerovar TyphimuriumADI activityMurine macrophagesVirulenceMutantsCertain pathogensExpressionControl of a Salmonella virulence locus by an ATP-sensing leader messenger RNA
Lee EJ, Groisman EA. Control of a Salmonella virulence locus by an ATP-sensing leader messenger RNA. Nature 2012, 486: 271-275. PMID: 22699622, PMCID: PMC3711680, DOI: 10.1038/nature11090.Peer-Reviewed Original ResearchMeSH Keywords5' Untranslated RegionsAdenosine TriphosphateAnimalsBacterial ProteinsBase SequenceCation Transport ProteinsFemaleGene Expression Regulation, BacterialHydrogen-Ion ConcentrationMacrophagesMiceMice, Inbred C3HMolecular Sequence DataMutationSalmonella InfectionsSalmonella typhimuriumSequence AlignmentVirulence
2010
An antisense RNA that governs the expression kinetics of a multifunctional virulence gene
Lee EJ, Groisman EA. An antisense RNA that governs the expression kinetics of a multifunctional virulence gene. Molecular Microbiology 2010, 76: 1020-1033. PMID: 20398218, PMCID: PMC2909850, DOI: 10.1111/j.1365-2958.2010.07161.x.Peer-Reviewed Original ResearchConceptsAntisense RNAGenome-wide transcriptome analysisRegulatory protein PhoPLong antisense RNAProtein levelsAntisense transcriptionMgtC proteinTranscriptome analysisRNase EAntisense transcriptsPolycistronic messageRNase IIISalmonella virulenceBacterial speciesPhysiological roleExpression kineticsTranscriptionRNAVirulence genesApparent roleVirulencePhoPSalmonella entericaMgtCAmgRS