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
Salmonella 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
Metabolic 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 analysis
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 componentCells
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
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 system
2006
A MyD88-Deficient Mouse Model Reveals a Role for Nramp1 in Campylobacter jejuni Infection
Watson RO, Novik V, Hofreuter D, Lara-Tejero M, Galán JE. A MyD88-Deficient Mouse Model Reveals a Role for Nramp1 in Campylobacter jejuni Infection. Infection And Immunity 2006, 75: 1994-2003. PMID: 17194808, PMCID: PMC1865720, DOI: 10.1128/iai.01216-06.Peer-Reviewed Original ResearchConceptsJejuni infectionAdaptor protein myeloid differentiation factor 88Myeloid differentiation factor 88Most Toll-like receptorsMyD88-deficient miceDifferentiation factor 88Campylobacter jejuni infectionAdult immunocompetent miceToll-like receptorsMajor worldwide causeFactor 88Immunocompetent miceMouse modelMouse susceptibilityEnteric illnessWorldwide causeJejuni colonizationInfectionMiceC. jejuniCampylobacter jejuniPotential roleVirulence genesBacterial pathogensIsogenic derivativesExpression of Interleukin-10 in Intestinal Lymphocytes Detected by an Interleukin-10 Reporter Knockin tiger Mouse
Kamanaka M, Kim ST, Wan YY, Sutterwala FS, Lara-Tejero M, Galán JE, Harhaj E, Flavell RA. Expression of Interleukin-10 in Intestinal Lymphocytes Detected by an Interleukin-10 Reporter Knockin tiger Mouse. Immunity 2006, 25: 941-952. PMID: 17137799, DOI: 10.1016/j.immuni.2006.09.013.Peer-Reviewed Original ResearchConceptsIntraepithelial lymphocytesInterleukin-10T cellsColonic lamina propria lymphocytesIL-10 protein expressionIL-10-producing T cellsSmall intestinal intraepithelial lymphocytesLamina propria lymphocytesRegulatory T cellsIntestinal intraepithelial lymphocytesAnti-CD3 treatmentIL-10 geneRegulation of inflammationRegulatory cells 1T cell receptor stimulationCell receptor stimulationIntestinal lymphocytesIL-10Receptor stimulationSmall intestineKnockin miceLymphocytesCells 1Protein expressionStrong expressionRole 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
2004
Rapid Development of T Cell Memory
Wong P, Lara-Tejero M, Ploss A, Leiner I, Pamer EG. Rapid Development of T Cell Memory. The Journal Of Immunology 2004, 172: 7239-7245. PMID: 15187098, DOI: 10.4049/jimmunol.172.12.7239.Peer-Reviewed Original ResearchConceptsMemory T cellsT cell populationsPrimary immune responseT cellsPrimary immunizationImmune responseMemory CD8 T cell responsesAg-specific CD8 T cellsCD8 T cell responsesEarly memory T cellsCD8 T cell populationsEffector T cell populationsPrime-boost immunizationPrime-boost vaccinationCD8 T cellsPrime-boost strategyT cell memoryT cell responsesCell populationsEarly time pointsProtective immunityAg doseCell memoryCell responsesImmunization