2024
Chaperone Hsp70 helps Salmonella survive infection-relevant stress by reducing protein synthesis
Chan C, Groisman E. Chaperone Hsp70 helps Salmonella survive infection-relevant stress by reducing protein synthesis. PLOS Biology 2024, 22: e3002560. PMID: 38574172, PMCID: PMC10994381, DOI: 10.1371/journal.pbio.3002560.Peer-Reviewed Original ResearchConceptsRibosome associationProtein synthesisProtein homeostasisS. typhimuriumProtein folding capacityPreventing protein aggregationC-terminal amino acidsDomains of lifeProtein synthesis in vitroInhibit protein synthesisFolding capacityHsp70 chaperonesJ-domainSynthesis in vitroProtein foldingReduction of protein synthesisChaperone Hsp70DnaKRibosomeProtein aggregationChaperoneAmino acidsProteinStarvationHSP70
2023
Correction for Duprey and Groisman, “FEDS: a Novel Fluorescence-Based High-Throughput Method for Measuring DNA Supercoiling In Vivo”
Duprey A, Groisman E. Correction for Duprey and Groisman, “FEDS: a Novel Fluorescence-Based High-Throughput Method for Measuring DNA Supercoiling In Vivo”. MBio 2023, 15: e02684-23. PMID: 38059645, PMCID: PMC10790772, DOI: 10.1128/mbio.02684-23.Peer-Reviewed Original ResearchAdvancing 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 ResearchAdvancing 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 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 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 ResearchConceptsMaster 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 genesChaperonesPhoPMutantsRibosomesOrganismsCSPCCellular Adaptations to Cytoplasmic Mg2+ Limitation
Groisman EA, Chan C. Cellular Adaptations to Cytoplasmic Mg2+ Limitation. Annual Review Of Microbiology 2021, 75: 649-672. PMID: 34623895, DOI: 10.1146/annurev-micro-020518-115606.Peer-Reviewed Original ResearchConceptsCytoplasmic MgLeader regionATP-dependent proteaseTranscriptional regulator PhoPAbundant divalent cationOpen reading frameActivity of ribosomesSimilar adaptation strategiesRegulated proteolysisExpression of proteinsRegulator PhoPMicrobial speciesReading frameCellular adaptationDifferent genesCoding regionsBacterial speciesProtein synthesisSpeciesProteinAbundanceDivalent cationsExpressionCytoplasmic Mg2Enzymatic reactionsThe regulation of DNA supercoiling across evolution
Duprey A, Groisman EA. The regulation of DNA supercoiling across evolution. Protein Science 2021, 30: 2042-2056. PMID: 34398513, PMCID: PMC8442966, DOI: 10.1002/pro.4171.Peer-Reviewed Original ResearchConceptsDomains of lifeDNA supercoilingCellular processesAbnormal DNA replicationCertain cellular processesActivity of topoisomerasesChromosome replicationGlobal supercoilingNegative supercoilsDNA replicationBiological questionsSupercoilingEukaryotic topoisomerasesTopoisomerasesSupercoilsSignificant therapeutic potentialOrganismsHelix structureBacteriaPhysicochemical factorsRegulationDouble helix structureReplicationUnique strategyArchaeaThe Practice of Science as the Pursuit of Knowledge.
Groisman EA. The Practice of Science as the Pursuit of Knowledge. The Yale Journal Of Biology And Medicine 2021, 94: 379-380. PMID: 34211357, PMCID: PMC8223544.Peer-Reviewed Original ResearchHow 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 ResearchConceptsBacterium 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 ResearchConceptsATP-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 ResearchConceptsE. 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 TyphimuriumVirulenceTranscriptionPromoterRegulator