Featured Publications
Developmental Transitions Coordinate Assembly of the Coxiella burnetii Dot/Icm Type IV Secretion System
Park D, Steiner S, Shao M, Roy CR, Liu J. Developmental Transitions Coordinate Assembly of the Coxiella burnetii Dot/Icm Type IV Secretion System. Infection And Immunity 2022, 90: e00410-22. PMID: 36190257, PMCID: PMC9584302, DOI: 10.1128/iai.00410-22.Peer-Reviewed Original ResearchConceptsSmall cell variantLarge cell variantDot/Icm type IV secretion systemCell variantIntracellular replicationActive large cell variantHost cellsIntracellular bacterial pathogenType IV secretion systemDot/Icm T4SSObligate intracellular bacterial pathogenC. burnetiiCoxiella burnetiiBiphasic developmental cycleUnique biphasic developmental cycleInfectionNew host cellsSecretion systemBacterial pathogensInfectious formHost vacuoleBurnetiiMorphological changesCellsLater stagesAnalysis of Dot/Icm Type IVB Secretion System Subassemblies by Cryoelectron Tomography Reveals Conformational Changes Induced by DotB Binding
Park D, Chetrit D, Hu B, Roy CR, Liu J. Analysis of Dot/Icm Type IVB Secretion System Subassemblies by Cryoelectron Tomography Reveals Conformational Changes Induced by DotB Binding. MBio 2020, 11: 10.1128/mbio.03328-19. PMID: 32071271, PMCID: PMC7029142, DOI: 10.1128/mbio.03328-19.Peer-Reviewed Original ResearchConceptsType IV secretion systemSecretion systemCryoelectron tomographyInner membraneDot/Icm apparatusConformational changesDot/IcmEukaryotic host cellsBacterial inner membraneWild-type cellsHost cell membraneWhole-cell contextMultiprotein nanomachineSubtomogram analysisSophisticated nanomachinesCytoplasmic substratesProtein effectorsCell polesDNA substratesSubtomogram averagingATPase complexDNA transferHost infectionStructural basisHost cellsA unique cytoplasmic ATPase complex defines the Legionella pneumophila type IV secretion channel
Chetrit D, Hu B, Christie PJ, Roy CR, Liu J. A unique cytoplasmic ATPase complex defines the Legionella pneumophila type IV secretion channel. Nature Microbiology 2018, 3: 678-686. PMID: 29784975, PMCID: PMC5970066, DOI: 10.1038/s41564-018-0165-z.Peer-Reviewed Original ResearchConceptsCytoplasmic complexType IV secretion channelType IV secretion systemInner membrane complexTranslocation of substratesCryo-electron tomographySecretion channelCell polesCytoplasmic ATPaseSecretion systemT4SS functionHexameric assemblyMembrane complexCytoplasmic channelsDNA complexesSubstrate transferT4SSChannel activationATPaseComplexesDistinct stagesAssemblyBiogenesisATPasesFurther analysisMultiple Legionella pneumophila effector virulence phenotypes revealed through high-throughput analysis of targeted mutant libraries
Shames SR, Liu L, Havey JC, Schofield WB, Goodman AL, Roy CR. Multiple Legionella pneumophila effector virulence phenotypes revealed through high-throughput analysis of targeted mutant libraries. Proceedings Of The National Academy Of Sciences Of The United States Of America 2017, 114: e10446-e10454. PMID: 29133401, PMCID: PMC5715750, DOI: 10.1073/pnas.1708553114.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBacterial ProteinsCytotoxicity, ImmunologicDisease Models, AnimalFemaleGene Expression Regulation, BacterialHigh-Throughput Nucleotide SequencingHost-Pathogen InteractionsHumansLegionella pneumophilaLegionnaires' DiseaseLoss of Function MutationMiceMice, Inbred C57BLMutagenesis, InsertionalPhenotypeVirulenceConceptsCultured host cellsHost cellsEffector proteinsHost immune systemFunction mutationsVirulence phenotypesSevere pneumoniaInfected miceBacterial clearanceEffector mutantsLarge cohortMouse modelDot/Icm type IV secretion systemImmune systemType IV secretion systemScreen resultsEffector protein activityDifferent effector proteinsGenetic complementation studiesLegionnaires' diseaseCausative agentHost pathogenesisDifferent virulence phenotypesInfectionDiseaseAMPylation Is Critical for Rab1 Localization to Vacuoles Containing Legionella pneumophila
Hardiman CA, Roy CR. AMPylation Is Critical for Rab1 Localization to Vacuoles Containing Legionella pneumophila. MBio 2014, 5: 10.1128/mbio.01035-13. PMID: 24520063, PMCID: PMC3950522, DOI: 10.1128/mbio.01035-13.Peer-Reviewed Original ResearchConceptsLCV membraneEffector proteinsGEF activityEndoplasmic reticulumIntracellular pathogen Legionella pneumophilaLegionella effector proteinsType IV secretion systemExchange factor domainLegionella pneumophilaMembrane-bound compartmentsMembrane-bound organellesPathogen Legionella pneumophilaAccumulation of GTPHost cell functionsAMPylation activityDrrA proteinRab1 proteinRab1 recruitmentLegionella effectorsNucleotidyltransferase domainAMPylationSecretion systemPosttranslational modificationsRab1GTPaseAnkyrin Repeat Proteins Comprise a Diverse Family of Bacterial Type IV Effectors
Pan X, Lührmann A, Satoh A, Laskowski-Arce MA, Roy CR. Ankyrin Repeat Proteins Comprise a Diverse Family of Bacterial Type IV Effectors. Science 2008, 320: 1651-1654. PMID: 18566289, PMCID: PMC2514061, DOI: 10.1126/science.1158160.Peer-Reviewed Original ResearchConceptsSecretion systemL. pneumophila-containing vacuoleIntracellular pathogen Legionella pneumophilaHost cellsDifferent bacterial proteinsType IV secretion systemMicrotubule-dependent vesicular transportEukaryotic host cellsType IV effectorsPathogen Legionella pneumophilaSpecialized secretion systemsAnkyrin Repeat ProteinsANK proteinsEukaryotic cellsHomology domainEffector proteinsEukaryotic factorsRepeat proteinsInfection of macrophagesVesicular transportBacterial proteinsLate endosomesDiverse familyProteinLegionella pneumophilaCaspase-11 stimulates rapid flagellin-independent pyroptosis in response to Legionella pneumophila
Case CL, Kohler LJ, Lima JB, Strowig T, de Zoete MR, Flavell RA, Zamboni DS, Roy CR. Caspase-11 stimulates rapid flagellin-independent pyroptosis in response to Legionella pneumophila. Proceedings Of The National Academy Of Sciences Of The United States Of America 2013, 110: 1851-1856. PMID: 23307811, PMCID: PMC3562791, DOI: 10.1073/pnas.1211521110.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Vesicular TransportAnimalsApoptosisApoptosis Regulatory ProteinsBone Marrow CellsCalcium-Binding ProteinsCARD Signaling Adaptor ProteinsCarrier ProteinsCaspase 1CaspasesCaspases, InitiatorCells, CulturedCytokinesCytoskeletal ProteinsEnzyme ActivationFlagellinHost-Pathogen InteractionsImmunoblottingLegionella pneumophilaMacrophagesMiceMice, Inbred C57BLMice, KnockoutMutationMyeloid Differentiation Factor 88NecrosisNLR Family, Pyrin Domain-Containing 3 ProteinReceptor, Interferon alpha-betaConceptsCaspase-11 activationCaspase-11Intracellular pathogen Legionella pneumophilaType IV secretion systemDot/IcmAdapter protein TRIFFunctional type IV secretion systemPathogen Legionella pneumophilaCaspase-1 activation pathwayNAIP/NLRC4Activation pathwayLegionella pneumophilaCaspase-11-dependent pyroptosisSecretion systemSevere defectsBacterial flagellinTreatment of macrophagesType I IFN receptorHost componentsIntracellular pathogensMicrobial signaturesPathwayIFN receptorCaspase-1Alternative pathway
2024
InSeq analysis of defined Legionella pneumophila libraries identifies a transporter-encoding gene cluster important for intracellular replication in mammalian hosts
Moss C, Roy C. InSeq analysis of defined Legionella pneumophila libraries identifies a transporter-encoding gene cluster important for intracellular replication in mammalian hosts. MBio 2024, 15: e01955-24. PMID: 39365064, PMCID: PMC11559062, DOI: 10.1128/mbio.01955-24.Peer-Reviewed Original ResearchMammalian hostsLegionella pneumophila</i>Mutant libraryIntracellular replicationDot/Icm type IV secretion systemHost cellsType IV secretion systemInfection of mammalian cellsTransposon insertion sequencingTransposon mutant libraryOpportunistic human pathogenIV secretion systemIsogenic deletion mutantsGenetic complementation studiesHost-pathogen interactionsIntracellular bacterial pathogensMultidrug efflux pumpsMammalian infection modelsATP-binding cassetteBacteria encounterDot/Icm systemSecretion systemTransposon sequencesGene clusterHost cytosol
2010
Inhibition of pathogen-induced apoptosis by a Coxiella burnetii type IV effector protein
Lührmann A, Nogueira CV, Carey KL, Roy CR. Inhibition of pathogen-induced apoptosis by a Coxiella burnetii type IV effector protein. Proceedings Of The National Academy Of Sciences Of The United States Of America 2010, 107: 18997-19001. PMID: 20944063, PMCID: PMC2973885, DOI: 10.1073/pnas.1004380107.Peer-Reviewed Original ResearchConceptsPathogen-induced apoptosisEffector proteinsMammalian hostsL. pneumophila effector proteinsType IV effector proteinsHost cellsType IV secretion systemMammalian host cellsL. pneumophilaGain of functionProtein repertoireOrganelle traffickingRepeat familyDistinct hostsSecretion systemInfection strategiesProtozoan hostsApoptosis pathwayIntracellular bacteriaIntracellular replicationVirulence determinantsProteinLegionella pneumophilaApoptosisPathogens