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 programInflammationVirulenceDietary sugars silence the master regulator of carbohydrate utilization in human gut Bacteroides species
Pearce V, Groisman E, Townsend G. Dietary sugars silence the master regulator of carbohydrate utilization in human gut Bacteroides species. Gut Microbes 2023, 15: 2221484. PMID: 37358144, PMCID: PMC10294740, DOI: 10.1080/19490976.2023.2221484.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBacteroidesDietary SugarsFructoseGastrointestinal MicrobiomeGlucoseHumansMammalsConceptsMaster regulatorMicrobial populationsOrthologous transcription factorsMammalian gut microbiotaMicrobial gene expressionHuman gut symbiontHuman gut BacteroidesDistinct microbial populationsIntestinal Bacteroides speciesGut symbiontsCarbohydrate utilizationMRNA leaderTranscription factorsHost dietGut BacteroidesNutrient availabilityGene expressionMolecular pathwaysUnknown mechanismDietary sugarsBacteroides speciesFuture therapeutic interventionsRegulatorSimple sugarsPathogenic outcomesBacteria 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 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
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 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 formPhoP
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 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 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 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
2016
Acidic 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
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 mutantsTraitsDiguanylateSpecies-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 activation