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 replicationBurnetiiA 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 systemHost SNAREs mediate fusion of vacuoles containing Legionella pneumophila with vesicles exiting the endoplasmic reticulum
Arasaki K, Roy C. Host SNAREs mediate fusion of vacuoles containing Legionella pneumophila with vesicles exiting the endoplasmic reticulum. The FASEB Journal 2009, 23: 867.4-867.4. DOI: 10.1096/fasebj.23.1_supplement.867.4.Peer-Reviewed Original ResearchPlasma membrane-derived vacuoleEarly secretory vesiclesSNARE complexSNARE proteinsSecretory vesiclesPlasma membrane t-SNAREFunctional SNARE complexesPlasma membrane syntaxinsEndoplasmic reticulum-derived vesiclesLegionella pneumophilaT-SNAREsSyntaxin 4Mechanism of fusionSpecialized organellesSyntaxin 2Syntaxin 3Mammalian cellsEndoplasmic reticulumSec22bSNAP23SyntaxinBacterial uptakeLocalization studiesIntracellular pathogensBacterial replicationThe 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 mechanismsResiduesPathogensATG3MicrobesAtg7CytosolVacuolesPathwayPneumophilaCaspase-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 pathwaySyntaxin 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
2019
Manipulation of Host Cell Organelles by Intracellular Pathogens
Omotade T, Roy C. Manipulation of Host Cell Organelles by Intracellular Pathogens. 2019, 179-196. DOI: 10.1128/9781683670261.ch13.Peer-Reviewed Original ResearchPathogen-containing vacuolesNascent phagosomesSpecialized organellesIntracellular pathogensHost cell organellesMembrane-bound compartmentsHost-pathogen interfaceMost microbesPhagosome maturationLysosomal degradationMembrane transportCell organellesOrganellesHost macrophagesPhagosomesMicrobesPathogensCompartmentsCoevolutionLysosomesVacuolesReplicationMaturationPhagocytosis