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 ResearchMechanisms of substrate recognition by a typhoid toxin secretion-associated muramidase
Geiger T, Lara-Tejero M, Xiong Y, Galán JE. Mechanisms of substrate recognition by a typhoid toxin secretion-associated muramidase. ELife 2020, 9: e53473. PMID: 31958059, PMCID: PMC6996933, DOI: 10.7554/elife.53473.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 ResearchAlternate 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 typhiThe 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 ResearchConceptsEffector 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 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
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 ResearchConceptsType 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 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 structuresN-terminal αNeedle tip complexSalmonella type III secretion systemDomain bindsHelical hairpinVirulence proteinsFusion proteinHuman cellsSteric clashesSipDProteinPathogenic bacteriaNMR modelsRecent NMRPrgIPrgI.Needle apparatusPRE methodSpecific regionsStructural componentsAssembly