Featured Publications
Multiple 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 phenotypesInfectionDiseaseThe Legionella Anti-autophagy Effector RavZ Targets the Autophagosome via PI3P- and Curvature-Sensing Motifs
Horenkamp FA, Kauffman KJ, Kohler LJ, Sherwood RK, Krueger KP, Shteyn V, Roy CR, Melia TJ, Reinisch KM. The Legionella Anti-autophagy Effector RavZ Targets the Autophagosome via PI3P- and Curvature-Sensing Motifs. Developmental Cell 2015, 34: 569-576. PMID: 26343456, PMCID: PMC4594837, DOI: 10.1016/j.devcel.2015.08.010.Peer-Reviewed Original ResearchConceptsATG8 proteinsIntracellular pathogen Legionella pneumophilaPre-autophagosomal structureAtg8/LC3 proteinsPathogen Legionella pneumophilaHigh-curvature membranesMembrane transport pathwaysCytosol of cellsEffector proteinsCatalytic domainHost cytosolRavZAutophagy proteinsLC3 proteinPathogenic microbesSubstrate affinityProteinIntermediate membraneLegionella pneumophilaAutophagosomesAutophagyCytosolTransport pathwaysInterfacial activationMembraneA 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 systemAMPylation 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 pneumophilaThe Coxiella burnetii effector EmcB is a deubiquitinase that inhibits RIG-I signaling
Duncan-Lowey J, Crabill E, Jarret A, Reed S, Roy C. The Coxiella burnetii effector EmcB is a deubiquitinase that inhibits RIG-I signaling. Proceedings Of The National Academy Of Sciences Of The United States Of America 2023, 120: e2217602120. PMID: 36893270, PMCID: PMC10089202, DOI: 10.1073/pnas.2217602120.Peer-Reviewed Original ResearchConceptsDot/Icm systemHost-adapted pathogenUbiquitin chainsI interferon productionType I interferon productionSecretion systemHost cytosolIcm systemInterferon productionProtein secretion systemBacterial secretion systemsAcid-inducible gene IHost surveillance systemImmune sensorsObligate intracellular pathogensInducible gene ICytosolic surveillance systemsProtective immune responseEffector proteinsSpecialized organellesVacuolar nicheInhibition of RIGInnate immune sensorsSurveillance systemMammalian hosts
2024
The T4bSS of Legionella features a two-step secretion pathway with an inner membrane intermediate for secretion of transmembrane effectors.
Malmsheimer S, Grin I, Bohn E, Franz-Wachtel M, Macek B, Sahr T, Smollich F, Chetrit D, Meir A, Roy C, Buchrieser C, Wagner S. The T4bSS of Legionella features a two-step secretion pathway with an inner membrane intermediate for secretion of transmembrane effectors. PLOS Pathogens 2024, 20: e1012118. PMID: 39546547, PMCID: PMC11602083, DOI: 10.1371/journal.ppat.1012118.Peer-Reviewed Original ResearchConceptsEukaryotic host cellsEffector proteinsMembrane intermediatesC-terminal secretion signalHost cellsSoluble effector proteinsCytoplasmic sideBacterial inner membraneMechanism of secretionSecretion systemSecretion signalPeriplasmic loopTransmembrane effectorSecretion pathwayT4BSSInner membraneSubcellular locationIntracellular survivalMembrane targetingProtein complexesEfficient translocationBacterial cellsProteomic analysisL. pneumophilaSecretion process
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