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 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
2021
How 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
How 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 deprivationEssentialityOrganismsCytoplasmProteinA 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 resistanceGenomeTolerance
2018
Lvr, 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
Navigating 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 ResearchPrioritization 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
2015
When Too Much ATP Is Bad for Protein Synthesis
Pontes MH, Sevostyanova A, Groisman EA. When Too Much ATP Is Bad for Protein Synthesis. Journal Of Molecular Biology 2015, 427: 2586-2594. PMID: 26150063, PMCID: PMC4531837, DOI: 10.1016/j.jmb.2015.06.021.Peer-Reviewed Original ResearchConceptsProtein synthesisStructure of ribosomesEnergy-dependent activitiesATP levelsRibosome productionCellular processesTranslation initiationCytoplasmic membraneEssential enzymeCellular ATPEnergy currencyLiving cellsATPCellsDivalent cationsCrucial roleTriphosphateRibosomesAminoacylationOrganismsNon-physiological increaseCofactorEnzymeBiochemistryCommon divalent cations
2014
Tuning 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
2012
An Allele of an Ancestral Transcription Factor Dependent on a Horizontally Acquired Gene Product
Chen HD, Jewett MW, Groisman EA. An Allele of an Ancestral Transcription Factor Dependent on a Horizontally Acquired Gene Product. PLOS Genetics 2012, 8: e1003060. PMID: 23300460, PMCID: PMC3531487, DOI: 10.1371/journal.pgen.1003060.Peer-Reviewed Original ResearchConceptsPolymyxin B resistanceGene productsTranscription of PmrAGene regulatory circuitsB resistanceSingle amino acid differenceAmino acid differencesPmrA proteinAncestral genomesAncestral genePmrD proteinRegulatory circuitsB alleleHorizontal transferGene expressionPhenotypic differencesAcid differencesGenesBiochemical propertiesBiofilm formationPmrAAllelesSalmonella entericaS. entericaProteinExpression 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 pathogensExpression
2010
Orphan and hybrid two-component system proteins in health and disease
Raghavan V, Groisman EA. Orphan and hybrid two-component system proteins in health and disease. Current Opinion In Microbiology 2010, 13: 226-231. PMID: 20089442, PMCID: PMC2861427, DOI: 10.1016/j.mib.2009.12.010.Peer-Reviewed Original ResearchConceptsTwo-component systemResponse regulatorSensor kinaseTwo-component system proteinsGut symbiont Bacteroides thetaiotaomicronOpportunistic pathogen Pseudomonas aeruginosaResponse regulator domainCognate response regulatorPhosphorylation-independent mannerPathogen Pseudomonas aeruginosaRegulator domainEukaryotic hostsMembrane-bound regulatorsExpression programsExpression of enzymesPhosphorylated stateBiosynthetic enzymesStreptomyces speciesSingle polypeptideBacterial interactionsSystem proteinsBacteroides thetaiotaomicronEnzymatic propertiesRegulatorCertain sugars
2009
Transcription factor function and promoter architecture govern the evolution of bacterial regulons
Perez JC, Groisman EA. Transcription factor function and promoter architecture govern the evolution of bacterial regulons. Proceedings Of The National Academy Of Sciences Of The United States Of America 2009, 106: 4319-4324. PMID: 19251636, PMCID: PMC2649204, DOI: 10.1073/pnas.0810343106.Peer-Reviewed Original ResearchConceptsRegulatory circuitsBacterial regulonsPhoP proteinRegulatory protein PhoPBacterial transcription factorsTranscription factor functionCis-regulatory elementsGene regulatory circuitsHorizontal gene transferPathogen Salmonella entericaPromoter architectureEvolutionary changeRelated organismsVirulence regulatorTranscription factorsRegulonPhenotypic differencesFactor functionGene transferYersinia pestisSalmonella entericaCore membersProteinEukaryotesPhoP
2006
Sensing by bacterial regulatory systems in host and non-host environments
Groisman EA, Mouslim C. Sensing by bacterial regulatory systems in host and non-host environments. Nature Reviews Microbiology 2006, 4: 705-709. PMID: 16894339, DOI: 10.1038/nrmicro1478.Peer-Reviewed Original Research
2005
Virulence and drug resistance roles of multidrug efflux systems of Salmonella enterica serovar Typhimurium
Nishino K, Latifi T, Groisman EA. Virulence and drug resistance roles of multidrug efflux systems of Salmonella enterica serovar Typhimurium. Molecular Microbiology 2005, 59: 126-141. PMID: 16359323, DOI: 10.1111/j.1365-2958.2005.04940.x.Peer-Reviewed Original ResearchConceptsDrug efflux systemsEfflux systemSalmonella virulenceEscherichia coli homologueToxic compound extrusionResponse regulator PhoPATP-binding cassette (ABC) superfamiliesPhoP/PhoQOuter membrane componentsAmino acid sequenceDrug resistance rolesTwo-component systemSalmonella enterica serovar TyphimuriumGram-negative speciesMultidrug efflux systemsSame operonEnterica serovar TyphimuriumRegulator PhoPCompound extrusionAcid sequenceMajor facilitatorEfflux system genesPromoter regionVirulence phenotypesMajor regulatorThe origin and evolution of human pathogens
Groisman EA, Casadesús J. The origin and evolution of human pathogens. Molecular Microbiology 2005, 56: 1-7. PMID: 15773974, DOI: 10.1111/j.1365-2958.2005.04564.x.Peer-Reviewed Original ResearchConceptsCreation of genesNon-host environmentsHuman pathogensRelated bacterial speciesCertain pathogensORFan genesHomologous genesCell surface modificationExpression of productsHousekeeping functionsRelated membersHost rangeColonization processTissue specificityPathogenicity islandSequence databasesCertain lociBacterial speciesGenesCell surfaceDisparate regulationGenetic originBacterial pathogensNew functionsGene variation
2004
Activation of the RcsC/YojN/RcsB phosphorelay system attenuates Salmonella virulence
Mouslim C, Delgado M, Groisman EA. Activation of the RcsC/YojN/RcsB phosphorelay system attenuates Salmonella virulence. Molecular Microbiology 2004, 54: 386-395. PMID: 15469511, DOI: 10.1111/j.1365-2958.2004.04293.x.Peer-Reviewed Original ResearchConceptsConstitutive mutantsSalmonella virulenceNon-phagocytic cellsPhosphorelay systemWild-type SalmonellaExpression of productsVirulence functionsFull virulenceSensor geneCps operonRcsBConstitutive activationSuccessful infectionVirulence attenuationGenesVirulence factorsAberrant expressionBacterial pathogensVirulenceMutantsHost tissuesExpressionLocation-dependent mannerMutationsAttenuation phenotype