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
The 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
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
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
Feedback Control of Two-Component Regulatory Systems
Groisman EA. Feedback Control of Two-Component Regulatory Systems. Annual Review Of Microbiology 2016, 70: 103-124. PMID: 27607549, PMCID: PMC8380452, DOI: 10.1146/annurev-micro-102215-095331.Peer-Reviewed Original ResearchAcidic 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
2013
Bacterial Mg2+ Homeostasis, Transport, and Virulence
Groisman EA, Hollands K, Kriner MA, Lee EJ, Park SY, Pontes MH. Bacterial Mg2+ Homeostasis, Transport, and Virulence. Annual Review Of Genetics 2013, 47: 625-646. PMID: 24079267, PMCID: PMC4059682, DOI: 10.1146/annurev-genet-051313-051025.Peer-Reviewed Original Research
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 arrangementTransductionKinaseReciprocal Control between a Bacterium's Regulatory System and the Modification Status of Its Lipopolysaccharide
Kato A, Chen HD, Latifi T, Groisman EA. Reciprocal Control between a Bacterium's Regulatory System and the Modification Status of Its Lipopolysaccharide. Molecular Cell 2012, 47: 897-908. PMID: 22921935, PMCID: PMC3465083, DOI: 10.1016/j.molcel.2012.07.017.Peer-Reviewed Original ResearchInhibition 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 systemIntrinsic Negative Feedback Governs Activation Surge in Two-Component Regulatory Systems
Yeo WS, Zwir I, Huang HV, Shin D, Kato A, Groisman EA. Intrinsic Negative Feedback Governs Activation Surge in Two-Component Regulatory Systems. Molecular Cell 2012, 45: 409-421. PMID: 22325356, PMCID: PMC3713471, DOI: 10.1016/j.molcel.2011.12.027.Peer-Reviewed Original Research
2010
Positive Autoregulation Shapes Response Timing and Intensity in Two-component Signal Transduction Systems
Mitrophanov AY, Hadley TJ, Groisman EA. Positive Autoregulation Shapes Response Timing and Intensity in Two-component Signal Transduction Systems. Journal Of Molecular Biology 2010, 401: 671-680. PMID: 20600106, PMCID: PMC2942797, DOI: 10.1016/j.jmb.2010.06.051.Peer-Reviewed Original ResearchOrphan 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 phaseDNABacteriaGramPositive feedback in cellular control systems
Mitrophanov AY, Groisman EA. Positive feedback in cellular control systems. BioEssays 2008, 30: 542-555. PMID: 18478531, PMCID: PMC2486260, DOI: 10.1002/bies.20769.Peer-Reviewed Original ResearchThe PhoQ/PhoP Regulatory Network of Salmonella enterica
Kato A, Groisman EA. The PhoQ/PhoP Regulatory Network of Salmonella enterica. Advances In Experimental Medicine And Biology 2008, 631: 7-21. PMID: 18792679, DOI: 10.1007/978-0-387-78885-2_2.Peer-Reviewed Original ResearchConceptsTwo-component regulatory systemPathogen Salmonella enterica serovar TyphimuriumEnteric pathogen Salmonella enterica serovar TyphimuriumDistinct expression levelsPhoQ/PhoPTwo-component systemSalmonella enterica serovar TyphimuriumBacterial cell surfacePhoQ proteinPhoP proteinResponse regulatorTranscriptional cascadeConnector proteinEnterica serovar TyphimuriumPromoter structureRegulatory networksTranscription factorsSalmonella genesRegulatory architectureSalmonella lifestyleMajor regulatorExpression propertiesCell surfaceModifies expressionRegulatory system
2007
A connector of two-component regulatory systems promotes signal amplification and persistence of expression
Kato A, Mitrophanov AY, Groisman EA. A connector of two-component regulatory systems promotes signal amplification and persistence of expression. Proceedings Of The National Academy Of Sciences Of The United States Of America 2007, 104: 12063-12068. PMID: 17615238, PMCID: PMC1924540, DOI: 10.1073/pnas.0704462104.Peer-Reviewed Original ResearchConceptsTwo-component regulatory systemBacterial signal transductionRegulatory systemPersistence of expressionSignal transductionGene transcriptionRegulatory architectureSmall proteinsSalmonella entericaPathwayFunctional characteristicsPmrDExpressionFunctional propertiesPhoP.AmplificationTranscriptionSignal amplificationTransductionGenesDominant formOrganismsProteinPersistenceEnterica
2006
Acid pH activation of the PmrA/PmrB two‐component regulatory system of Salmonella enterica
Perez JC, Groisman EA. Acid pH activation of the PmrA/PmrB two‐component regulatory system of Salmonella enterica. Molecular Microbiology 2006, 63: 283-293. PMID: 17229213, PMCID: PMC1804205, DOI: 10.1111/j.1365-2958.2006.05512.x.Peer-Reviewed Original ResearchConceptsGlutamic acid residuesPmrA/PmrB systemAcid residuesTwo-component regulatory systemPathogen Salmonella enterica serovar TyphimuriumResponse regulator PmrATranscription of genesPmrA/PmrBSalmonella enterica serovar TyphimuriumPmrA proteinPolymyxin B resistancePeriplasmic domainWild-type SalmonellaEnterica serovar TyphimuriumGene productsGene expressionAnimal hostsRegulatory systemB resistanceSerovar TyphimuriumTranscriptionSalmonella entericaCellular changesGenesPH activationSensing 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