2020
Itaconate is an effector of a Rab GTPase cell-autonomous host defense pathway against Salmonella
Chen M, Sun H, Boot M, Shao L, Chang SJ, Wang W, Lam TT, Lara-Tejero M, Rego EH, Galán JE. Itaconate is an effector of a Rab GTPase cell-autonomous host defense pathway against Salmonella. Science 2020, 369: 450-455. PMID: 32703879, PMCID: PMC8020367, DOI: 10.1126/science.aaz1333.Peer-Reviewed Original Research
2019
High-resolution view of the type III secretion export apparatus in situ reveals membrane remodeling and a secretion pathway
Butan C, Lara-Tejero M, Li W, Liu J, Galán JE. High-resolution view of the type III secretion export apparatus in situ reveals membrane remodeling and a secretion pathway. Proceedings Of The National Academy Of Sciences Of The United States Of America 2019, 116: 24786-24795. PMID: 31744874, PMCID: PMC6900529, DOI: 10.1073/pnas.1916331116.Peer-Reviewed Original ResearchRole of SpaO in the assembly of the sorting platform of a Salmonella type III secretion system
Lara-Tejero M, Qin Z, Hu B, Butan C, Liu J, Galán JE. Role of SpaO in the assembly of the sorting platform of a Salmonella type III secretion system. PLOS Pathogens 2019, 15: e1007565. PMID: 30668610, PMCID: PMC6358110, DOI: 10.1371/journal.ppat.1007565.Peer-Reviewed Original Research
2018
Visualization of the type III secretion mediated Salmonella–host cell interface using cryo-electron tomography
Park D, Lara-Tejero M, Waxham MN, Li W, Hu B, Galán JE, Liu J. Visualization of the type III secretion mediated Salmonella–host cell interface using cryo-electron tomography. ELife 2018, 7: e39514. PMID: 30281019, PMCID: PMC6175578, DOI: 10.7554/elife.39514.Peer-Reviewed Original ResearchConceptsCryo-electron tomographyEffector translocationBacterial-host cell contactType III protein secretion systemProtein secretion systemHost cell interfaceProtein secretion machinesCell membraneComplex host-pathogen interactionsType III secretionHost-pathogen interactionsHost cell membraneTarget cell membraneNegative bacterial pathogensTranslocon poreSecretion machineEffector proteinsSecretion systemHost cellsBacterial pathogensCell contactCell interfaceIntimate associationTranslocationBacteriaSalmonella stimulates pro-inflammatory signalling through p21-activated kinases bypassing innate immune receptors
Sun H, Kamanova J, Lara-Tejero M, Galán JE. Salmonella stimulates pro-inflammatory signalling through p21-activated kinases bypassing innate immune receptors. Nature Microbiology 2018, 3: 1122-1130. PMID: 30224799, PMCID: PMC6158040, DOI: 10.1038/s41564-018-0246-z.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBacterial LoadCdc42 GTP-Binding ProteinCells, CulturedHost-Pathogen InteractionsHumansImmunity, InnateIntestinesMAP Kinase Kinase KinasesMiceNF-kappa BP21-Activated KinasesPhosphorylationSalmonella InfectionsSalmonella typhimuriumSignal TransductionTNF Receptor-Associated Factor 6Type III Secretion SystemsConceptsP21-activated kinase 1TNF receptor-associated factor 6Innate immune receptorsImmune receptorsType III protein secretion systemMitogen-activated protein kinase kinase kinase 7Protein kinase kinase kinase 7Protein secretion systemPro-inflammatory signalingP21-activated kinaseNegative regulatory mechanismsEnteric pathogen Salmonella typhimuriumPathogen Salmonella typhimuriumIntestinal inflammationMicrobial productsEffector proteinsS. typhimuriumSecretion systemInflammatory signalingRegulatory mechanismsKinase 1Kinase 7PAK inhibitorsCritical downstreamResident microbiota
2017
Visualization and characterization of individual type III protein secretion machines in live bacteria
Zhang Y, Lara-Tejero M, Bewersdorf J, Galán JE. Visualization and characterization of individual type III protein secretion machines in live bacteria. Proceedings Of The National Academy Of Sciences Of The United States Of America 2017, 114: 6098-6103. PMID: 28533372, PMCID: PMC5468683, DOI: 10.1073/pnas.1705823114.Peer-Reviewed Original ResearchConceptsProtein secretion machinesSecretion machineType III secretion machinesLive bacteriaEukaryotic cellsEffector proteinsMolecular machinesSubcellular distributionSuperresolution microscopyBacteriaMajor insightsResolution gapDetailed viewAssemblyMutantsProteinNanomachinesCharacterizationCellsSpatial distributionIsolationIn Situ Molecular Architecture of the Salmonella Type III Secretion Machine
Hu B, Lara-Tejero M, Kong Q, Galán JE, Liu J. In Situ Molecular Architecture of the Salmonella Type III Secretion Machine. Cell 2017, 168: 1065-1074.e10. PMID: 28283062, PMCID: PMC5393631, DOI: 10.1016/j.cell.2017.02.022.Peer-Reviewed Original ResearchMeSH KeywordsBacterial ProteinsBacterial Secretion SystemsCryoelectron MicroscopyProtein TransportSalmonella typhimuriumVirulenceConceptsType III secretion machinesSecretion machineNeedle complexType III protein secretion systemCytoplasmic sorting platformProtein secretion systemMulti-protein machinesProtein secretion machinesTarget eukaryotic cellsCryo-electron tomographyDifferent deletion mutantsSub-tomogram averagingSignificant conformational changesMolecular architectureExport apparatusEukaryotic cellsSecretion systemDeletion mutantsSorting platformConformational changesSitu structureMajor insightsMolecular modelingStructural componentsAssembly
2016
The Salmonella Effector Protein SopA Modulates Innate Immune Responses by Targeting TRIM E3 Ligase Family Members
Kamanova J, Sun H, Lara-Tejero M, Galán JE. The Salmonella Effector Protein SopA Modulates Innate Immune Responses by Targeting TRIM E3 Ligase Family Members. PLOS Pathogens 2016, 12: e1005552. PMID: 27058235, PMCID: PMC4825927, DOI: 10.1371/journal.ppat.1005552.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBacterial ProteinsCell LineDisease Models, AnimalGene Knockout TechniquesHost-Parasite InteractionsHumansImmunity, InnateImmunoprecipitationMass SpectrometryMiceReal-Time Polymerase Chain ReactionSalmonella InfectionsSalmonella typhimuriumSignal TransductionUbiquitin-Protein LigasesConceptsInflammatory responseImmune responseSalmonella typhimurium infectionInnate immune receptorsInnate immune responseHECT-type E3 ligaseTyphimurium infectionAnimal modelsIntestinal epitheliumIntestinal tractImmune receptorsInflammationStimulationTRIM56Type III secretion systemMDA5Pathogenicity island 1Family membersEfficient stimulationSalmonella typhimuriumIsland 1ResponseE3 ubiquitin ligasesInfectionSecretion systemA Family of Salmonella Type III Secretion Effector Proteins Selectively Targets the NF-κB Signaling Pathway to Preserve Host Homeostasis
Sun H, Kamanova J, Lara-Tejero M, Galán JE. A Family of Salmonella Type III Secretion Effector Proteins Selectively Targets the NF-κB Signaling Pathway to Preserve Host Homeostasis. PLOS Pathogens 2016, 12: e1005484. PMID: 26933955, PMCID: PMC4775039, DOI: 10.1371/journal.ppat.1005484.Peer-Reviewed Original ResearchConceptsNF-κBHost homeostasisNF-κB Signaling PathwayHost innate immune responsePro-inflammatory cytokinesInnate immune responseType III secretion effector proteinsHost tissue damageIntestinal inflammationSalmonella typhimurium strainsImmune responseAnimal modelsInflammationRelB transcription factorPathogen replicationMicrobial infectionsTyphimurium strainsEffector proteinsSignaling pathwaysType III secretion systemInfectionBacterial pathogensBacteria Salmonella typhimuriumSignal transduction pathwaysSalmonella typhimuriumA Bacterial Pathogen Targets a Host Rab-Family GTPase Defense Pathway with a GAP
Spanò S, Gao X, Hannemann S, Lara-Tejero M, Galán JE. A Bacterial Pathogen Targets a Host Rab-Family GTPase Defense Pathway with a GAP. Cell Host & Microbe 2016, 19: 216-226. PMID: 26867180, PMCID: PMC4854434, DOI: 10.1016/j.chom.2016.01.004.Peer-Reviewed Original ResearchConceptsAntimicrobial defenseCell-autonomous defense mechanismS. typhi infectionHuman pathogen Salmonella typhiExchange factor BLOC-3Host defense pathwaysTyphi infectionType III secretion effectorsIntracellular pathogensPotential broad roleVacuolar pathogensSalmonella typhiPotent strategySalmonella effectorsBacterial pathogensMiceS. typhimuriumDefense pathwaysDefense mechanismsPathogen targetsPathogensEffectorsPathwayBroader roleBLOC-3
2014
NMR Model of PrgI–SipD Interaction and Its Implications in the Needle-Tip Assembly of the Salmonella Type III Secretion System
Rathinavelan T, Lara-Tejero M, Lefebre M, Chatterjee S, McShan AC, Guo DC, Tang C, Galan JE, De Guzman RN. NMR Model of PrgI–SipD Interaction and Its Implications in the Needle-Tip Assembly of the Salmonella Type III Secretion System. Journal Of Molecular Biology 2014, 426: 2958-2969. PMID: 24951833, PMCID: PMC4108505, DOI: 10.1016/j.jmb.2014.06.009.Peer-Reviewed Original ResearchConceptsType III secretion systemTip proteinSecretion systemRecent atomic structuresN-terminal αNeedle tip complexSalmonella type III secretion systemDomain bindsHelical hairpinVirulence proteinsFusion proteinHuman cellsSteric clashesSipDProteinPathogenic bacteriaNMR modelsRecent NMRPrgIPrgI.Needle apparatusPRE methodSpecific regionsStructural componentsAssembly
2013
Engineering the type III secretion system in non-replicating bacterial minicells for antigen delivery
Carleton HA, Lara-Tejero M, Liu X, Galán JE. Engineering the type III secretion system in non-replicating bacterial minicells for antigen delivery. Nature Communications 2013, 4: 1590. PMID: 23481398, PMCID: PMC3693737, DOI: 10.1038/ncomms2594.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigensBacterial ProteinsBacterial Secretion SystemsCD8-Positive T-LymphocytesGenetic EngineeringMiceMice, Inbred C57BLOvalbuminSalmonella typhimuriumConceptsBacterial minicellsPresentation pathwayVaccine developmentClass IAntigen-specific CD8Antigen delivery platformSalmonella typhimurium type III secretion systemDelivery platformType III secretion systemCellular immunotherapyT cellsAntigen deliveryImmune responseHeterologous antigensProtein antigensSecretion systemCertain populationsAntigenNanoparticlesDeliveryNanomachinesCD8ImmunotherapyPathwayNovel approach
2011
A Sorting Platform Determines the Order of Protein Secretion in Bacterial Type III Systems
Lara-Tejero M, Kato J, Wagner S, Liu X, Galán JE. A Sorting Platform Determines the Order of Protein Secretion in Bacterial Type III Systems. Science 2011, 331: 1188-1191. PMID: 21292939, PMCID: PMC3859126, DOI: 10.1126/science.1201476.Peer-Reviewed Original ResearchConceptsSecretion systemSorting platformType III protein secretion systemBacterial type III protein secretion systemsType III protein secretionProtein secretionType III secretion systemCytoplasmic sorting platformProtein secretion systemType III systemSalmonella enterica serovar TyphimuriumNovel antimicrobial strategiesEukaryotic cellsEffector proteinsEnterica serovar TyphimuriumCellular processesSerovar TyphimuriumImportant pathogenProteinAntimicrobial strategiesChaperonesSecretionPathogensMechanismSubstrate
2010
Organization and coordinated assembly of the type III secretion export apparatus
Wagner S, Königsmaier L, Lara-Tejero M, Lefebre M, Marlovits TC, Galán JE. Organization and coordinated assembly of the type III secretion export apparatus. Proceedings Of The National Academy Of Sciences Of The United States Of America 2010, 107: 17745-17750. PMID: 20876096, PMCID: PMC2955140, DOI: 10.1073/pnas.1008053107.Peer-Reviewed Original ResearchConceptsExport apparatusNeedle complexType III protein secretion systemType III secretion machinesBacterial effector proteinsProtein secretion systemType III secretion export apparatusCryo-electron microscopyBacterial nanomachinesSecretion machineSymbiotic bacteriaEukaryotic cellsEffector proteinsSecretion systemMembrane proteinsApparatus componentsSubstantial coordinationBase assemblyProteinAssemblyEssential componentInsectsOrganellesComplexesBiology
2009
Salmonella Typhimurium Type III Secretion Effectors Stimulate Innate Immune Responses in Cultured Epithelial Cells
Bruno VM, Hannemann S, Lara-Tejero M, Flavell RA, Kleinstein SH, Galán JE. Salmonella Typhimurium Type III Secretion Effectors Stimulate Innate Immune Responses in Cultured Epithelial Cells. PLOS Pathogens 2009, 5: e1000538. PMID: 19662166, PMCID: PMC2714975, DOI: 10.1371/journal.ppat.1000538.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBacterial ProteinsBlotting, WesternCell LineColitisEpithelial CellsGene ExpressionGene Expression ProfilingGuanine Nucleotide Exchange FactorsHumansImmunity, InnateMiceMitogen-Activated Protein Kinase KinasesMyotonin-Protein KinaseNF-kappa BOligonucleotide Array Sequence AnalysisProtein Serine-Threonine KinasesReverse Transcriptase Polymerase Chain ReactionSalmonella InfectionsSalmonella typhimuriumSignal TransductionTranscription, GeneticConceptsInnate immune receptorsInnate immune responseIntestinal inflammationImmune responseEpithelial cellsBacterial productsIntestinal inflammatory pathologyImmune receptorsCultured epithelial cellsEnteric pathogen Salmonella typhimuriumInnate immune systemIntestinal epithelial cellsInflammatory pathologyInflammatory responseType III secretion effectorsImmune systemSalmonella typhimuriumNF-kappaBMitogen-activated protein kinaseEnteric pathogensPathogen Salmonella typhimuriumPathologyReceptorsInflammationType III secretion systemSalmonella enterica Serovar Typhimurium Pathogenicity Island 1-Encoded Type III Secretion System Translocases Mediate Intimate Attachment to Nonphagocytic Cells
Lara-Tejero M, Galán JE. Salmonella enterica Serovar Typhimurium Pathogenicity Island 1-Encoded Type III Secretion System Translocases Mediate Intimate Attachment to Nonphagocytic Cells. Infection And Immunity 2009, 77: 2635-2642. PMID: 19364837, PMCID: PMC2708559, DOI: 10.1128/iai.00077-09.Peer-Reviewed Original ResearchMeSH KeywordsAntigens, BacterialBacterial AdhesionBacterial ProteinsCell LineEpithelial CellsGene DeletionGenomic IslandsHumansMembrane ProteinsSalmonella typhimuriumConceptsType III secretion systemPathogenicity island 1Secretion systemMammalian cellsIntimate associationIsland 1Host cellsBacterial contactBacterial surfaceIntimate attachmentS. typhimurium mutantsProtein translocasesBacterial proteinsMolecular basisTTSS componentsTarget cellsNonphagocytic cellsTyphimurium mutantsImmunofluorescence microscopyDifferent bacteriaTranslocasesSalmonella entericaSipBBacteriaProtein
2006
Assembly of the inner rod determines needle length in the type III secretion injectisome
Marlovits TC, Kubori T, Lara-Tejero M, Thomas D, Unger VM, Galán JE. Assembly of the inner rod determines needle length in the type III secretion injectisome. Nature 2006, 441: 637-640. PMID: 16738660, DOI: 10.1038/nature04822.Peer-Reviewed Original ResearchRole of the caspase-1 inflammasome in Salmonella typhimurium pathogenesis
Lara-Tejero M, Sutterwala FS, Ogura Y, Grant EP, Bertin J, Coyle AJ, Flavell RA, Galán J. Role of the caspase-1 inflammasome in Salmonella typhimurium pathogenesis. Journal Of Experimental Medicine 2006, 203: 1407-1412. PMID: 16717117, PMCID: PMC2118315, DOI: 10.1084/jem.20060206.Peer-Reviewed Original ResearchCritical Role for NALP3/CIAS1/Cryopyrin in Innate and Adaptive Immunity through Its Regulation of Caspase-1
Sutterwala FS, Ogura Y, Szczepanik M, Lara-Tejero M, Lichtenberger GS, Grant EP, Bertin J, Coyle AJ, Galán JE, Askenase PW, Flavell RA. Critical Role for NALP3/CIAS1/Cryopyrin in Innate and Adaptive Immunity through Its Regulation of Caspase-1. Immunity 2006, 24: 317-327. PMID: 16546100, DOI: 10.1016/j.immuni.2006.02.004.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine TriphosphateAnimalsApoptosis Regulatory ProteinsAutoimmune DiseasesCARD Signaling Adaptor ProteinsCarrier ProteinsCaspase 1Cytoskeletal ProteinsEnzyme ActivationImmunity, InnateInterleukin-1LipopolysaccharidesMacrophagesMiceMice, Inbred C57BLNLR Family, Pyrin Domain-Containing 3 ProteinRNA, MessengerSalmonella typhimuriumShock, SepticToll-Like ReceptorsConceptsIL-1betaImpaired contact hypersensitivity responseCaspase-1NALP3-deficient miceContact hypersensitivity responseFamilial cold autoinflammatory syndromeCytokines IL-1alphaCaspase-1 functionMuckle-Wells syndromeCaspase-1 activationLipopolysaccharide-stimulated macrophagesContact hypersensitivityHypersensitivity responseIL-18Articular syndromeAutoinflammatory disordersAutoinflammatory syndromesIL-1alphaAdaptive immunityAdaptor molecule ASCCaspase-1 activation pathwayNALP3SyndromeActivation pathwayMice