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 ResearchThe Type III Secretion System Sorting Platform
Lara-Tejero M. The Type III Secretion System Sorting Platform. Current Topics In Microbiology And Immunology 2019, 427: 133-142. PMID: 31183608, DOI: 10.1007/82_2019_167.Peer-Reviewed Original ResearchConceptsSecretion machineSecretion systemType III secretion injectisomeSecretion processType III secretion systemLarge cytoplasmic complexesProtein secretion machinesHost plasma membraneProtein translocasesCytoplasmic complexSecretion pathwayNeedle complexSorting platformPlasma membraneHost cellsProteinTranslocasesInjectisomeComplexesEffectorsPathwayComplex substructureSubstrateMembraneAssemblyThe Injectisome, a Complex Nanomachine for Protein Injection into Mammalian Cells
Lara-Tejero M, Galán JE. The Injectisome, a Complex Nanomachine for Protein Injection into Mammalian Cells. EcoSal Plus 2019, 8: 10.1128/ecosalplus.esp-0039-2018. PMID: 30942149, PMCID: PMC6450406, DOI: 10.1128/ecosalplus.esp-0039-2018.Peer-Reviewed Original ResearchMeSH KeywordsBacterial ProteinsEukaryotic CellsGram-Negative BacteriaHost-Pathogen InteractionsProtein TransportType III Secretion SystemsVirulence FactorsConceptsEffector proteinsGram-negative bacteriaSecretion systemBacterial envelopeType III protein secretion systemProtein secretion systemHost cellular functionsEukaryotic plasma membraneEukaryotic cell membranesHost cell cytosolMultiprotein nanomachineEukaryotic hostsComplex nanomachinesImportant bacterial pathogensCellular functionsMammalian cellsNeedle complexOuter membranePlasma membraneCell cytosolInjectisomeCell membraneProteinBacterial pathogensCentral roleRole 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 associationTranslocationBacteriaPeptidoglycan editing by a specific ld-transpeptidase controls the muramidase-dependent secretion of typhoid toxin
Geiger T, Pazos M, Lara-Tejero M, Vollmer W, Galán JE. Peptidoglycan editing by a specific ld-transpeptidase controls the muramidase-dependent secretion of typhoid toxin. Nature Microbiology 2018, 3: 1243-1254. PMID: 30250245, PMCID: PMC7464686, DOI: 10.1038/s41564-018-0248-x.Peer-Reviewed Original ResearchConceptsProtein export mechanismProtein secretion mechanismsTyphoid toxinEssential virulence factorBacterial poleMammalian cellsPeptidoglycan layerMost bacterial pathogensOuter membraneExport mechanismSecretion mechanismToxin secretionBacterial speciesTranslocation processTrans sideVirulence factorsBacterial pathogensExtracellular spaceTransport pathwaysTarget cellsToxinTyphoid feverCellsSubsequent releaseSecretion
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 distributionIsolationMetabolic and fitness determinants for in vitro growth and intestinal colonization of the bacterial pathogen Campylobacter jejuni
Gao B, Vorwerk H, Huber C, Lara-Tejero M, Mohr J, Goodman AL, Eisenreich W, Galán JE, Hofreuter D. Metabolic and fitness determinants for in vitro growth and intestinal colonization of the bacterial pathogen Campylobacter jejuni. PLOS Biology 2017, 15: e2001390. PMID: 28542173, PMCID: PMC5438104, DOI: 10.1371/journal.pbio.2001390.Peer-Reviewed Original ResearchMeSH KeywordsAbsorption, PhysiologicalAmino AcidsAnimalsAnti-Bacterial AgentsBacterial ProteinsCampylobacter InfectionsCampylobacter jejuniCation Transport ProteinsDNA Transposable ElementsDysbiosisGastroenteritisGene DeletionGenetic Association StudiesGenome, BacterialGenomic LibraryMice, Inbred C57BLMicrobial ViabilityModels, BiologicalMutagenesis, InsertionalMutationConceptsCampylobacter jejuniFood-producing animalsInfectious causesFood-borne illnessMost infectionsMouse modelHuman infectionsIntestinal colonizationIntestinal tractInfectionJejuni colonizationMouse intestineNext-generation sequencingIntracellular ion homeostasisC. jejuniFitness determinantsCertain nutrientsPathogenic strainsJejuniMetabolic requirementsComprehensive genome-wide analysisBacterial pathogen Campylobacter jejuniPathogen Campylobacter jejuniAnimalsGenome-wide analysisIn 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
Novel Components of the Flagellar System in Epsilonproteobacteria
Gao B, Lara-Tejero M, Lefebre M, Goodman AL, Galán JE. Novel Components of the Flagellar System in Epsilonproteobacteria. MBio 2014, 5: 10.1128/mbio.01349-14. PMID: 24961693, PMCID: PMC4073491, DOI: 10.1128/mbio.01349-14.Peer-Reviewed Original ResearchConceptsBacterial pathogen Campylobacter jejuniPathogen Campylobacter jejuniFlagellar systemBacterial speciesNovel componentGenetic screenFlagellar structureMost bacteriaMolecular basisHigh-throughput genetic screensFlagellar apparatusComprehensive genetic screenDiverse bacterial speciesCampylobacter jejuniDifferent bacterial speciesGroup of bacteriaBacterial poleBacterial organellesFlagellar machineryTransposon mutagenesisNext-generation sequencingEpsilonproteobacteriaFlagellaRecent studiesSpeciesBacterial Type III Secretion Systems: Specialized Nanomachines for Protein Delivery into Target Cells
Galán JE, Lara-Tejero M, Marlovits TC, Wagner S. Bacterial Type III Secretion Systems: Specialized Nanomachines for Protein Delivery into Target Cells. Annual Review Of Microbiology 2014, 68: 1-24. PMID: 25002086, PMCID: PMC4388319, DOI: 10.1146/annurev-micro-092412-155725.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBacteriaBacterial InfectionsBacterial ProteinsBacterial Secretion SystemsHumansProtein TransportConceptsEukaryotic cellsEffector proteinsBacterial envelopeType III secretion systemTarget eukaryotic cellsComplex nanomachinesNovel antimicrobial strategiesPathogen's benefitCellular functionsSecretion systemNeedle complexBacterial pathogenesisCytoplasmic componentsSpecialized nanomachinesSpecific substratesProteinPlantsCentral roleProtein deliveryAntimicrobial strategiesBacteriaNanomachinesTarget cellsCentral componentCellsNMR 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 ResearchConceptsBacterial 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 ResearchConceptsType 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