2023
Dietary 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 outcomes
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 TyphimuriumVirulenceTranscriptionPromoterRegulatorThe 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 entericaGenes
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
2013
The Biology of the PmrA/PmrB Two-Component System: The Major Regulator of Lipopolysaccharide Modifications
Chen HD, Groisman EA. The Biology of the PmrA/PmrB Two-Component System: The Major Regulator of Lipopolysaccharide Modifications. Annual Review Of Microbiology 2013, 67: 83-112. PMID: 23799815, PMCID: PMC8381567, DOI: 10.1146/annurev-micro-092412-155751.Peer-Reviewed Original ResearchConceptsPmrA/PmrBTwo-component systemPmrA/PmrB systemMajor regulatorEnteric pathogen Salmonella entericaGene expression outputPathogen Salmonella entericaTranscriptional regulatorsExpression outputEcological nichesOuter membraneRelated bacteriaLPS modificationsExtent bacteriaLipopolysaccharide modificationDifferential survivalRegulatorHost immune systemNegative bacteriaSalmonella entericaBacteriaBiologyPmrBQuantitative differencesImmune system
2012
Intramolecular arrangement of sensor and regulator overcomes relaxed specificity in hybrid two-component systems
Townsend GE, Raghavan V, Zwir I, Groisman EA. Intramolecular arrangement of sensor and regulator overcomes relaxed specificity in hybrid two-component systems. Proceedings Of The National Academy Of Sciences Of The United States Of America 2012, 110: e161-e169. PMID: 23256153, PMCID: PMC3545799, DOI: 10.1073/pnas.1212102110.Peer-Reviewed Original ResearchConceptsTwo-component regulatory systemResponse regulatorSensor kinasePhosphotransfer specificityRelaxed specificityTwo-component systemHuman gut symbiont Bacteroides thetaiotaomicronGut symbiont Bacteroides thetaiotaomicronRR pairsCognate response regulatorCognate protein partnersRegulatory systemProtein partnersTransduce signalsCellular processesSignal transductionSingle polypeptidePhosphoryl transferNoncognate proteinsBacteroides thetaiotaomicronSpecific interactionsRegulatorIntramolecular arrangementTransductionKinaseInhibition of Bacterial Virulence: Drug‐Like Molecules Targeting the Salmonella enterica PhoP Response Regulator
Tang YT, Gao R, Havranek JJ, Groisman EA, Stock AM, Marshall GR. Inhibition of Bacterial Virulence: Drug‐Like Molecules Targeting the Salmonella enterica PhoP Response Regulator. Chemical Biology & Drug Design 2012, 79: 1007-1017. PMID: 22339993, PMCID: PMC3445336, DOI: 10.1111/j.1747-0285.2012.01362.x.Peer-Reviewed Original ResearchConceptsTwo-component signal transductionResponse regulatorPhoP response regulatorHistidine kinaseBacterial virulenceGene expressionSensor histidine kinaseVirulence gene regulationSignal transduction systemSignal transduction pathwaysExpression of genesTCST systemsStructure-based virtual screeningGene regulationSignal transductionTranscription factorsTransduction pathwaysTransduction systemVirtual screeningBiophysical assaysAntibacterial developmentMode of actionExternal signalsRegulatorRegulatory system
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
Response Acceleration in Post-translationally Regulated Genetic Circuits
Mitrophanov AY, Groisman EA. Response Acceleration in Post-translationally Regulated Genetic Circuits. Journal Of Molecular Biology 2009, 396: 1398-1409. PMID: 19932119, PMCID: PMC2861412, DOI: 10.1016/j.jmb.2009.11.043.Peer-Reviewed Original ResearchConceptsRegulatory proteinsTwo-component system familyBacterial signal transductionGenetic regulatory circuitsTwo-component systemSteady-state output levelGenetic circuitsRegulatory circuitsSignal transductionSensor proteinsTranscription factorsGene expressionLiving cellsPhosphorylation levelsProteinSpecific signalsKinetic propertiesSuch modificationsCellsTransductionPhosphorylationRegulatorMechanismPrevalent formExpression
2008
Signal integration in bacterial two-component regulatory systems
Mitrophanov AY, Groisman EA. Signal integration in bacterial two-component regulatory systems. Genes & Development 2008, 22: 2601-2611. PMID: 18832064, PMCID: PMC2751022, DOI: 10.1101/gad.1700308.Peer-Reviewed Original ResearchConceptsTwo-component systemResponse regulatorTwo-component regulatory systemSignal integrationBacterial signal transductionGram-negative bacteriaCellular processesSignal transductionPhosphorylated statePhosphorylation statePhysiological functionsSpecific functionsRegulatory systemBiochemical reactionsKey mediatorRegulatorPhosphorelayAntibiotic resistanceDifferent mechanismsSporulationTransductionStationary phaseDNABacteriaGram
2004
Connecting two-component regulatory systems by a protein that protects a response regulator from dephosphorylation by its cognate sensor
Kato A, Groisman EA. Connecting two-component regulatory systems by a protein that protects a response regulator from dephosphorylation by its cognate sensor. Genes & Development 2004, 18: 2302-2313. PMID: 15371344, PMCID: PMC517523, DOI: 10.1101/gad.1230804.Peer-Reviewed Original ResearchMeSH KeywordsAllelesBacterial ProteinsBase SequenceGene Expression Regulation, BacterialMagnesiumMolecular Sequence DataPhosphorylationPromoter Regions, GeneticProtein Processing, Post-TranslationalProtein Structure, TertiarySalmonella entericaSignal TransductionTranscription FactorsTranscription, GeneticConceptsTwo-component systemResponse regulatorPhosphorylated formTwo-component regulatory systemTranscription of PmrAResponse regulator PmrAPhoP/PhoQPmrA/PmrBPmrA proteinTarget promotersCognate sensorProtein bindsSignal transductionCellular responsesDephosphorylationRegulatory systemPmrAProteinTranscriptionMultiple signalsRegulatorHigh affinityPmrA.Fundamental questionsPhoP
2003
Making informed decisions: regulatory interactions between two-component systems
Bijlsma JJ, Groisman EA. Making informed decisions: regulatory interactions between two-component systems. Trends In Microbiology 2003, 11: 359-366. PMID: 12915093, DOI: 10.1016/s0966-842x(03)00176-8.Peer-Reviewed Original ResearchConceptsTwo-component systemTwo-component regulatory systemPost-transcriptional mechanismsMultitude of stressesResponse regulatorBacterial adaptationRegulatory interactionsComplex nichePhosphoryl transferMolecular levelRegulatory systemSpecific signalsMultiple signalsPhosphorelayMultifaceted environmentNicheRegulatorBacteriaPhosphataseMechanismStressAdaptation
2002
Fe(III)‐mediated cellular toxicity
Chamnongpol S, Dodson W, Cromie MJ, Harris ZL, Groisman EA. Fe(III)‐mediated cellular toxicity. Molecular Microbiology 2002, 45: 711-719. PMID: 12139617, DOI: 10.1046/j.1365-2958.2002.03041.x.Peer-Reviewed Original ResearchConceptsIsogenic wild-type strainSignal transduction systemWild-type strainGram-negative speciesPmrA mutantOuter membraneIron-mediated toxicityTransduction systemMicrobicidal activityBacterial survivalMajor regulatorCell deathPmrA geneIron homeostasisMutantsEscherichia coliSalmonella mutantsDeleterious metalsCellular toxicitySalmonella entericaExcellent biocatalystAnaerobic conditionsGenesRegulatorSpecies
2000
Acetyl phosphate-dependent activation of a mutant PhoP response regulator that functions independently of its cognate sensor kinase11Edited by M. Gottesman
Chamnongpol S, Groisman E. Acetyl phosphate-dependent activation of a mutant PhoP response regulator that functions independently of its cognate sensor kinase11Edited by M. Gottesman. Journal Of Molecular Biology 2000, 300: 291-305. PMID: 10873466, DOI: 10.1006/jmbi.2000.3848.Peer-Reviewed Original ResearchMeSH KeywordsAllelesAmino Acid SubstitutionBacterial ProteinsEnvironmentGene Expression Regulation, BacterialGenes, BacterialGenes, RegulatorMagnesiumMembrane ProteinsMethyl-Accepting Chemotaxis ProteinsModels, MolecularMutationOperonOrganophosphatesPhosphorylationProtein BindingProtein BiosynthesisProtein Structure, TertiaryRecombinant Fusion ProteinsSalmonella entericaTrans-ActivatorsTranscription, GeneticConceptsTranscription of PhoPResponse regulatorAcetyl phosphateResponse regulator receiver domainSites of phosphorylationVirulence gene expressionPhoP response regulatorTwo-component systemPhoQ proteinPhoP proteinReceiver domainSensor kinaseTranscriptional repressionCognate sensorMutant proteinsM. GottesmanPhosphorylated stateAspartate residueGene expressionPhoPTranscriptionPhosphate donorRegulatorProteinSalmonella enterica