Featured Publications
Host cell depletion of tryptophan by IFNγ-induced Indoleamine 2,3-dioxygenase 1 (IDO1) inhibits lysosomal replication of Coxiella burnetii
Ganesan S, Roy CR. Host cell depletion of tryptophan by IFNγ-induced Indoleamine 2,3-dioxygenase 1 (IDO1) inhibits lysosomal replication of Coxiella burnetii. PLOS Pathogens 2019, 15: e1007955. PMID: 31461509, PMCID: PMC6736304, DOI: 10.1371/journal.ppat.1007955.Peer-Reviewed Original ResearchConceptsC. burnetiiC. burnetii replicationIntracellular replicationIntracellular pathogensPro-inflammatory cytokine interferon gammaIFNγ-induced genesCell-autonomous defense mechanismAbsence of IFNγCytokine interferon-gammaMost intracellular pathogensMacrophage-like cellsKynurenine metabolitesCell depletionEffector mechanismsPathogen Coxiella burnetiiInterferon gammaIFNγTryptophan availabilityHost defenseDioxygenase 1Coxiella burnetiiTHP1 cellsRestrict replicationBacterial replicationBurnetiiAMPylation 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 modificationsRab1GTPasePathogen signatures activate a ubiquitination pathway that modulates the function of the metabolic checkpoint kinase mTOR
Ivanov SS, Roy CR. Pathogen signatures activate a ubiquitination pathway that modulates the function of the metabolic checkpoint kinase mTOR. Nature Immunology 2013, 14: 1219-1228. PMID: 24121838, PMCID: PMC3839319, DOI: 10.1038/ni.2740.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBase SequenceCell LineCells, CulturedCytokinesEukaryotic Initiation Factor-4EGene ExpressionHost-Pathogen InteractionsImmunoblottingLegionella pneumophilaLegionnaires' DiseaseMacrophagesMiceMolecular Sequence DataMutationProto-Oncogene Proteins c-aktReverse Transcriptase Polymerase Chain ReactionRNA InterferenceSignal TransductionTOR Serine-Threonine KinasesUbiquitinationAsc and Ipaf Inflammasomes Direct Distinct Pathways for Caspase-1 Activation in Response to Legionella pneumophila
Case CL, Shin S, Roy CR. Asc and Ipaf Inflammasomes Direct Distinct Pathways for Caspase-1 Activation in Response to Legionella pneumophila. Infection And Immunity 2009, 77: 1981-1991. PMID: 19237518, PMCID: PMC2681768, DOI: 10.1128/iai.01382-08.Peer-Reviewed Original ResearchCaspase-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
2000
Identification and Subcellular Localization of the Legionella pneumophila IcmX Protein: a Factor Essential for Establishment of a Replicative Organelle in Eukaryotic Host Cells
Matthews M, Roy C. Identification and Subcellular Localization of the Legionella pneumophila IcmX Protein: a Factor Essential for Establishment of a Replicative Organelle in Eukaryotic Host Cells. Infection And Immunity 2000, 68: 3971-3982. PMID: 10858211, PMCID: PMC101675, DOI: 10.1128/iai.68.7.3971-3982.2000.Peer-Reviewed Original ResearchConceptsEukaryotic host cellsReplicative organelleGene productsHost cellsSecretion apparatusDot/Icm proteinsDot/icm genesWild-type L. pneumophilaL. pneumophila chromosomePathogen Legionella pneumophilaHost cell parasitismImmunoblot analysisMurine bone marrow-derived macrophagesL. pneumophilaConjugal transfer systemObvious orthologsBone marrow-derived macrophagesIcm genesBacterial periplasmCell parasitismMammalian macrophagesDeletion mutantsSubcellular localizationPhagosome biogenesisMarrow-derived macrophagesExploitation of macrophages as a replication niche by Legionella pneumophila: Response
Roy C, Coers J. Exploitation of macrophages as a replication niche by Legionella pneumophila: Response. Trends In Microbiology 2000, 8: 49-50. PMID: 10664593, DOI: 10.1016/s0966-842x(99)01673-x.Peer-Reviewed Original Research
1999
Modulation of phagosome biogenesis by Legionella pneumophila creates an organelle permissive for intracellular growth
Coers J, Monahan C, Roy C. Modulation of phagosome biogenesis by Legionella pneumophila creates an organelle permissive for intracellular growth. Nature Cell Biology 1999, 1: 451-453. PMID: 10559990, DOI: 10.1038/15687.Peer-Reviewed Original ResearchPore‐forming activity is not sufficient for Legionella pneumophila phagosome trafficking and intracellular growth
Zuckman D, Hung J, Roy C. Pore‐forming activity is not sufficient for Legionella pneumophila phagosome trafficking and intracellular growth. Molecular Microbiology 1999, 32: 990-1001. PMID: 10361301, DOI: 10.1046/j.1365-2958.1999.01410.x.Peer-Reviewed Original ResearchConceptsPhagosome traffickingPhagosome-lysosome fusionIntracellular growthLysosome fusionEukaryotic cellular processesInsertion of poresPore-forming activityL. pneumophila mutantsHost cell cytoplasmCellular processesMammalian cellsReplicative nicheSimilar cytolytic activityGene productsPhagosome membraneIntracellular bacteriaTraffickingCell cytoplasmEffector moleculesBacterial pathogensLegionella pneumophilaMacrophage membraneVirulent bacteriaBacteriaFusion inhibition
1998
Legionella pneumophila DotA protein is required for early phagosome trafficking decisions that occur within minutes of bacterial uptake
Roy C, Berger K, Isberg R. Legionella pneumophila DotA protein is required for early phagosome trafficking decisions that occur within minutes of bacterial uptake. Molecular Microbiology 1998, 28: 663-674. PMID: 9632267, DOI: 10.1046/j.1365-2958.1998.00841.x.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigens, CDBacterial ProteinsCell LineFluorescent Antibody TechniqueGTP-Binding ProteinsHumansLegionella pneumophilaLysosome-Associated Membrane GlycoproteinsLysosomesMacrophagesMembrane FusionMembrane GlycoproteinsMembrane ProteinsMiceMutationPhagosomesPlasmidsRab GTP-Binding ProteinsRab7 GTP-Binding ProteinsConceptsDotA mutantsL. pneumophila phagosomeLAMP-1DotA proteinL. pneumophilaMembrane-bound compartmentsLysosomal glycoprotein LAMP-1Bacterial pathogensIntracellular bacterial pathogenReplicative phagosomeSmall GTPVacuolar membraneEndocytic pathwayProtein Rab7Fusion eventsMutant bacteriaMolecular basisGenetic studiesBacterial uptakeMutantsPhagosomesTrafficking profilesContinuous expressionIntracellular sitesMacrophage uptake
1997
Topology of Legionella pneumophila DotA: an inner membrane protein required for replication in macrophages
Roy C, Isberg R. Topology of Legionella pneumophila DotA: an inner membrane protein required for replication in macrophages. Infection And Immunity 1997, 65: 571-578. PMID: 9009315, PMCID: PMC176098, DOI: 10.1128/iai.65.2.571-578.1997.Peer-Reviewed Original ResearchConceptsDotA mutantsAmino acidsMembrane proteinsIntegral cytoplasmic membrane proteinLarge periplasmic domainInner membrane proteinCarboxyl-terminal cytoplasmic domainIntracellular growthCytoplasmic membrane proteinAlkaline phosphatase fusionsL. pneumophila pathogenesisIntracellular growth defectMembrane-spanning domainsStructure-function analysisProtein fractionation studiesPeriplasmic domainDotA proteinTranslational fusionGrowth defectCytoplasmic domainInner membraneHybrid proteinCytoplasmic regionDotA geneC-terminus