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 replicationBurnetiiMultiple 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 phenotypesInfectionDiseaseA Screen of Coxiella burnetii Mutants Reveals Important Roles for Dot/Icm Effectors and Host Autophagy in Vacuole Biogenesis
Newton HJ, Kohler LJ, McDonough JA, Temoche-Diaz M, Crabill E, Hartland EL, Roy CR. A Screen of Coxiella burnetii Mutants Reveals Important Roles for Dot/Icm Effectors and Host Autophagy in Vacuole Biogenesis. PLOS Pathogens 2014, 10: e1004286. PMID: 25080348, PMCID: PMC4117601, DOI: 10.1371/journal.ppat.1004286.Peer-Reviewed Original ResearchConceptsHost autophagyTransposon insertionDot/Icm effectorsDot/Icm systemAutophagosome protein LC3Intracellular growth defectPathogen-occupied vacuolesTransposon insertion mutantsVacuole biogenesisEffector proteinsInsertion mutantsModification enzymesGrowth defectArrayed libraryCentral metabolismIcm systemMutantsMolecular mechanismsVisual screenProtein LC3Host cellsIntracellular replicationGenesIntracellular pathogensRegulatory systemThe Machinery at Endoplasmic Reticulum-Plasma Membrane Contact Sites Contributes to Spatial Regulation of Multiple Legionella Effector Proteins
Hubber A, Arasaki K, Nakatsu F, Hardiman C, Lambright D, De Camilli P, Nagai H, Roy CR. The Machinery at Endoplasmic Reticulum-Plasma Membrane Contact Sites Contributes to Spatial Regulation of Multiple Legionella Effector Proteins. PLOS Pathogens 2014, 10: e1004222. PMID: 24992562, PMCID: PMC4081824, DOI: 10.1371/journal.ppat.1004222.Peer-Reviewed Original ResearchLegionella pneumophila proteins that regulate Rab1 membrane cycling
Ingmundson A, Delprato A, Lambright DG, Roy CR. Legionella pneumophila proteins that regulate Rab1 membrane cycling. Nature 2007, 450: 365-369. PMID: 17952054, DOI: 10.1038/nature06336.Peer-Reviewed Original ResearchConceptsDrrA proteinRab1 functionMembrane cyclingGTPase-activating protein activityIntracellular pathogen Legionella pneumophilaRecruitment of Rab1Pathogen-occupied vacuolesPathogen Legionella pneumophilaDistinct biochemical reactionsL. pneumophilaLegionella pneumophilaRab1 activityRab1 activationRab proteinsEukaryotic cellsExchange factorGTP hydrolysisProtein activityRab1Membrane functionBacterial replicationProteinBiochemical reactionsPneumophilaVacuolesAnkyrin 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 pneumophilaModulation of Rab GTPase function by a protein phosphocholine transferase
Mukherjee S, Liu X, Arasaki K, McDonough J, Galán JE, Roy CR. Modulation of Rab GTPase function by a protein phosphocholine transferase. Nature 2011, 477: 103-106. PMID: 21822290, PMCID: PMC3206611, DOI: 10.1038/nature10335.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBacterial ProteinsChlorocebus aethiopsCOS CellsDiacylglycerol CholinephosphotransferaseGuanine Nucleotide Exchange FactorsHEK293 CellsHost-Pathogen InteractionsHumansLegionella pneumophilaLegionnaires' DiseaseMass SpectrometryProtein Processing, Post-TranslationalRab GTP-Binding ProteinsThe Legionella pneumophila Effector DrrA Is Sufficient to Stimulate SNARE-Dependent Membrane Fusion
Arasaki K, Toomre DK, Roy CR. The Legionella pneumophila Effector DrrA Is Sufficient to Stimulate SNARE-Dependent Membrane Fusion. Cell Host & Microbe 2012, 11: 46-57. PMID: 22264512, PMCID: PMC3266541, DOI: 10.1016/j.chom.2011.11.009.Peer-Reviewed Original ResearchConceptsMembrane transport pathwaysEndoplasmic reticulumSyntaxin proteinsFusion of ERMembrane fusionSNARE-dependent membrane fusionBacterial pathogen Legionella pneumophilaPathogen-containing vacuolesSNARE protein Sec22bIntracellular bacterial pathogen Legionella pneumophilaPathogen Legionella pneumophilaFusion of vesiclesRab1 activationNoncanonical pairingTransport pathwaysRab1 GTPasePlasma membraneVesicle fusionOrganellesDrrASec22bVesiclesLegionella pneumophilaProteinVacuolesThe Legionella Effector RavZ Inhibits Host Autophagy Through Irreversible Atg8 Deconjugation
Choy A, Dancourt J, Mugo B, O’Connor T, Isberg RR, Melia TJ, Roy CR. The Legionella Effector RavZ Inhibits Host Autophagy Through Irreversible Atg8 Deconjugation. Science 2012, 338: 1072-1076. PMID: 23112293, PMCID: PMC3682818, DOI: 10.1126/science.1227026.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAutophagyAutophagy-Related Protein 7Autophagy-Related Protein 8 FamilyAutophagy-Related ProteinsBacterial ProteinsCell Culture TechniquesCysteine ProteasesGene DeletionGlycineHEK293 CellsHost-Pathogen InteractionsHumansHydrolysisLegionella pneumophilaLegionnaires' DiseaseMicrofilament ProteinsPhagosomesUbiquitin-Activating EnzymesUbiquitin-Conjugating EnzymesConceptsATG8 proteinsIntracellular pathogen Legionella pneumophilaPathogen Legionella pneumophilaAdjacent aromatic residuesCarboxyl-terminal glycine residueAutophagosome membraneEukaryotic cellsAutophagy pathwayGlycine residueAromatic residuesIntracellular pathogensRavZAutophagyProteinLegionella pneumophilaSpecific mechanismsResiduesPathogensATG3MicrobesAtg7CytosolVacuolesPathwayPneumophilaSyntaxin 11 Contributes to the Interferon-Inducible Restriction of Coxiella burnetii Intracellular Infection
Ganesan S, Alvarez N, Steiner S, Fowler K, Corona A, Roy C. Syntaxin 11 Contributes to the Interferon-Inducible Restriction of Coxiella burnetii Intracellular Infection. MBio 2023, 14: e03545-22. PMID: 36728431, PMCID: PMC9972978, DOI: 10.1128/mbio.03545-22.Peer-Reviewed Original ResearchConceptsC. burnetii replicationSNARE proteinsHost cellsSyntaxin-11Cell-autonomous responsesIntracellular pathogensMembrane fusion eventsLysosome-derived organellesDefense mechanismsModel bacterial pathogenMultiple cell typesEukaryotic cellsDefense pathwaysDelivery of cargoReplication of pathogensHuman proteinsFusion eventsDissemination of pathogensFusion pathwayHost proteinsIntrinsic defense mechanismsHost vesiclesHost restriction factorsStable expressionSubcellular organelles
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
2006
NALP3: a key player in caspase-1 activation
Sutterwala F, Ogura Y, Zamboni D, Roy C, Flavell R. NALP3: a key player in caspase-1 activation. Innate Immunity 2006, 12: 251-256. PMID: 16953978, DOI: 10.1177/09680519060120040701.Peer-Reviewed Original ResearchConceptsNLR familyCell death pathwaysNLR family membersAdaptor molecule ASCPro-inflammatory caspasesMultiprotein complexesDeath pathwaysPathogen recognitionCaspase-1 activationKey playersRecent findingsCaspase-1Family membersAuto-inflammatory syndromeActivationAuto-inflammatory disordersFamilyCaspasesGenesMuckle-Wells syndromeBiologyImmune responseProteinMembersFamilial cold auto-inflammatory syndrome
2001
How the parasitic bacterium Legionella pneumophila modifies its phagosome and transforms it into rough ER: implications for conversion of plasma membrane to the ER membrane.
Tilney L, Harb O, Connelly P, Robinson C, Roy C. How the parasitic bacterium Legionella pneumophila modifies its phagosome and transforms it into rough ER: implications for conversion of plasma membrane to the ER membrane. Journal Of Cell Science 2001, 114: 4637-50. PMID: 11792828, DOI: 10.1242/jcs.114.24.4637.Peer-Reviewed Original ResearchMeSH KeywordsBacterial ProteinsCarrier ProteinsCell FractionationCell MembraneGram-Positive BacteriaHumansIntracellular MembranesLegionella pneumophilaLipid MetabolismLysosomesMembrane ProteinsMicroscopy, ElectronMitochondriaMolecular ChaperonesMutationOrganellesPhagosomesRibosomesTime FactorsU937 CellsConceptsPhagosomal membraneRough endoplasmic reticulumRough ERL. pneumophilaL. pneumophila mutantsBacterium Legionella pneumophilaMinutes of infectionLegionella pneumophilaInfected macrophagesER membraneCellular processesMitochondrial membranePlasma membraneER vesiclesEndoplasmic reticulumMacrophage infectionPhagosomesLack of cholesterolMitochondriaPneumophilaMembraneTiny hairsERMutants
2000
Identification of Icm protein complexes that play distinct roles in the biogenesis of an organelle permissive for Legionella pneumophila intracellular growth
Coers J, Kagan J, Matthews M, Nagai H, Zuckman D, Roy C. Identification of Icm protein complexes that play distinct roles in the biogenesis of an organelle permissive for Legionella pneumophila intracellular growth. Molecular Microbiology 2000, 38: 719-736. PMID: 11115108, DOI: 10.1046/j.1365-2958.2000.02176.x.Peer-Reviewed Original ResearchConceptsPhagosome traffickingTransport apparatusHost cellsProtein-protein interactionsSubset of genesGel overlay analysisDistinct phenotypic categoriesPhagocytic host cellsIcm genesTranslocation channelReplicative organelleTwo-hybridProtein complexesSpecialized organellesTransporter functionIntracellular growthMolecular levelDistinct rolesVirulence determinantsGenesPore formationBacterial pathogensBiogenesisPhenotypic categoriesLegionella pneumophilaIdentification 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
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
1996
Use of Salt to Isolate Legionella pneumophila Mutants Unable to Replicate in Macrophages
VOGEL J, ROY C, ISBERG R. Use of Salt to Isolate Legionella pneumophila Mutants Unable to Replicate in Macrophages. Annals Of The New York Academy Of Sciences 1996, 797: 271-272. PMID: 8993377, DOI: 10.1111/j.1749-6632.1996.tb52975.x.Peer-Reviewed Original Research
1993
Legionella pneumophila: factors involved in the route and response to an intracellular niche.
Isberg R, Rankin S, Roy C, Swanson M, Berger K. Legionella pneumophila: factors involved in the route and response to an intracellular niche. Infectious Agents And Disease 1993, 2: 220-3. PMID: 8173798.Peer-Reviewed Original Research