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
Alternate subunit assembly diversifies the function of a bacterial toxin
Fowler CC, Stack G, Jiao X, Lara-Tejero M, Galán JE. Alternate subunit assembly diversifies the function of a bacterial toxin. Nature Communications 2019, 10: 3684. PMID: 31417089, PMCID: PMC6695444, DOI: 10.1038/s41467-019-11592-0.Peer-Reviewed Original ResearchInvestigation of the role of typhoid toxin in acute typhoid fever in a human challenge model
Gibani MM, Jones E, Barton A, Jin C, Meek J, Camara S, Galal U, Heinz E, Rosenberg-Hasson Y, Obermoser G, Jones C, Campbell D, Black C, Thomaides-Brears H, Darlow C, Dold C, Silva-Reyes L, Blackwell L, Lara-Tejero M, Jiao X, Stack G, Blohmke CJ, Hill J, Angus B, Dougan G, Galán J, Pollard AJ. Investigation of the role of typhoid toxin in acute typhoid fever in a human challenge model. Nature Medicine 2019, 25: 1082-1088. PMID: 31270506, PMCID: PMC6892374, DOI: 10.1038/s41591-019-0505-4.Peer-Reviewed Original ResearchConceptsHuman challenge modelTyphoid toxinChallenge modelTyphoid feverAcute typhoid feverDuration of bacteremiaFurther clinical dataS. typhiAcute infectionOral challengeClinical syndromeChronic infectionBacterial carriageClinical dataSevere diseaseTN groupFever symptomsHealthy volunteersDisease pathogenesisTyphoid infectionTyphoid diseaseColony-forming unitsHost-restricted pathogenInfectionSalmonella typhi
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 releaseSecretionSalmonella 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
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
Bacterial 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 ResearchConceptsEukaryotic 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 structuresNeedle tip complexN-terminal αSalmonella type III secretion systemDomain bindsHelical hairpinVirulence proteinsFusion proteinHuman cellsSteric clashesSipDProteinPathogenic bacteriaNMR modelsRecent NMRPrgIPrgI.Needle apparatusPRE methodSpecific regionsStructural componentsAssembly
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
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 Research
2004
A New Twist in the Hijacking of the Actin-Nucleating Machinery
Lara-Tejero M, Galán JE. A New Twist in the Hijacking of the Actin-Nucleating Machinery. Molecular Cell 2004, 15: 495-497. PMID: 15327766, DOI: 10.1016/j.molcel.2004.08.013.Peer-Reviewed Original Research