2024
Dual roles for a tick protein disulfide isomerase during the life cycle of the Lyme disease agent.
Tang X, Cui Y, Namarra U, Tian X, Rivas-Giorgi F, Fikrig E. Dual roles for a tick protein disulfide isomerase during the life cycle of the Lyme disease agent. MBio 2024, e0175424. PMID: 39470213, DOI: 10.1128/mbio.01754-24.Peer-Reviewed Original ResearchProtein disulfide isomeraseLyme disease agentDisulfide isomeraseBlood-feeding vectorsExtracellular pathogensGene expressionInvasion of host cellsThiol-disulfide oxidoreductasesDisease agentsGroup of enzymesStages of bacterial infectionVirulence factorsLife cycleChaperone activityMammalian hostsHost cellsBlood-feeding ticksIsomeraseMicrobial infectionsColonized ticksPathogensDiverse infectionsMicrobial invasionInfection of miceVector-borne diseases
2021
Aedes aegypti SNAP and a calcium transporter ATPase influence dengue virus dissemination
Marin-Lopez A, Jiang J, Wang Y, Cao Y, MacNeil T, Hastings AK, Fikrig E. Aedes aegypti SNAP and a calcium transporter ATPase influence dengue virus dissemination. PLOS Neglected Tropical Diseases 2021, 15: e0009442. PMID: 34115766, PMCID: PMC8195420, DOI: 10.1371/journal.pntd.0009442.Peer-Reviewed Original ResearchConceptsSalivary gland proteinsSuccessful viral transmissionNew mammalian hostDengue virusWild habitatsHabitat expansionGland proteinsA. aegypti vectorMammalian hostsUbiquitous expressionDENV infectionGene expressionMosquito midgutProtein componentsATPase proteinVector proteinProteinSalivary glandsBlood mealViral cycleAedes aegypti mosquitoesSusceptible hostsAedes aegyptiMosquitoesHost
2017
Multiple UBXN family members inhibit retrovirus and lentivirus production and canonical NFκΒ signaling by stabilizing IκBα
Hu Y, O’Boyle K, Auer J, Raju S, You F, Wang P, Fikrig E, Sutton RE. Multiple UBXN family members inhibit retrovirus and lentivirus production and canonical NFκΒ signaling by stabilizing IκBα. PLOS Pathogens 2017, 13: e1006187. PMID: 28152074, PMCID: PMC5308826, DOI: 10.1371/journal.ppat.1006187.Peer-Reviewed Original ResearchConceptsGene expressionHundreds of genesCycle assaysNFκB pathwayCo-immunoprecipitation studiesMouse embryo fibroblastsDownstream effector functionsJurkat T cellsPrimary human fibroblastsEmbryonic lethalityFamily membersUBA domainUBXN1HIV gene expressionSingle-cycle assaysProtein turnoverEmbryo fibroblastsCell adhesionGlobal regulationCanonical NFκB pathwayNFκB signalingHuman fibroblastsLike receptorsPathwayKnockdown
2016
A novel mosquito ubiquitin targets viral envelope protein for degradation and reduces virion production during dengue virus infection
Troupin A, Londono-Renteria B, Conway MJ, Cloherty E, Jameson S, Higgs S, Vanlandingham DL, Fikrig E, Colpitts TM. A novel mosquito ubiquitin targets viral envelope protein for degradation and reduces virion production during dengue virus infection. Biochimica Et Biophysica Acta 2016, 1860: 1898-1909. PMID: 27241849, PMCID: PMC4949077, DOI: 10.1016/j.bbagen.2016.05.033.Peer-Reviewed Original ResearchConceptsProtein degradationUbiquitin proteinGene expressionProtein expression constructsSite-directed mutagenesisViral protein degradationInnate immune signalingDengue virusProteasomal degradationProtein interactionsExpression constructsMosquito cellsSignificant human diseaseMicroarray analysisImmune signalingViral envelope proteinsVirus infectionHuman diseasesBlood feedingAmino acidsProteinMultiple functionsQRT-PCRVirion productionAntiviral function
2013
Identification of Genes Critical for Resistance to Infection by West Nile Virus Using RNA-Seq Analysis
Qian F, Chung L, Zheng W, Bruno V, Alexander RP, Wang Z, Wang X, Kurscheid S, Zhao H, Fikrig E, Gerstein M, Snyder M, Montgomery RR. Identification of Genes Critical for Resistance to Infection by West Nile Virus Using RNA-Seq Analysis. Viruses 2013, 5: 1664-1681. PMID: 23881275, PMCID: PMC3738954, DOI: 10.3390/v5071664.Peer-Reviewed Original ResearchConceptsCommon gene pathwaysNovel cellular responsesDifferential gene expressionRNA-seq analysisWest Nile virusGene expression analysisPrimary human macrophagesGene isoformsHigh-throughput methodRNA-seqGene pathwaysExpression analysisGenes CriticalKnock-downGene expressionCellular responsesGene changesResistant individualsBiological settingsHuman macrophagesGenesCritical roleAvailable treatmentsHealthy donorsViral infectionThe lipoprotein La7 contributes to Borrelia burgdorferi persistence in ticks and their transmission to naïve hosts
Yang X, Hegde S, Shroder DY, Smith AA, Promnares K, Neelakanta G, Anderson JF, Fikrig E, Pal U. The lipoprotein La7 contributes to Borrelia burgdorferi persistence in ticks and their transmission to naïve hosts. Microbes And Infection 2013, 15: 729-737. PMID: 23774694, PMCID: PMC3769513, DOI: 10.1016/j.micinf.2013.06.001.Peer-Reviewed Original ResearchConceptsComplex enzootic cycleInner membrane proteinB. burgdorferi persistenceProtein-protein interactionsOuter membrane lipoproteinNaïve hostsSpirochete life cycleCo-immunoprecipitation studiesMammalian infectivityMembrane proteinsRedundant rolesMolecular detailsMammalian hostsMembrane lipoproteinGene expressionWild typeInfection cycleLiquid chromatography-mass spectrometry analysisPathogen survivalBiological significanceHost transmissionEnzootic cyclePathogen transmissionSpectrometry analysisLA7
2012
Ixodes scapularis JAK-STAT Pathway Regulates Tick Antimicrobial Peptides, Thereby Controlling the Agent of Human Granulocytic Anaplasmosis
Liu L, Dai J, Zhao YO, Narasimhan S, Yang Y, Zhang L, Fikrig E. Ixodes scapularis JAK-STAT Pathway Regulates Tick Antimicrobial Peptides, Thereby Controlling the Agent of Human Granulocytic Anaplasmosis. The Journal Of Infectious Diseases 2012, 206: 1233-1241. PMID: 22859824, PMCID: PMC3448968, DOI: 10.1093/infdis/jis484.Peer-Reviewed Original ResearchConceptsJAK-STAT pathwayTick salivary glandsA. phagocytophilum infectionAntimicrobial peptidesElectrophoretic mobility shift assaysPeptide-encoding genesMobility shift assaysPhagocytophilum infectionHuman granulocytic anaplasmosisGene familyTransducer activatorMammalian hostsRNA interferenceShift assaysTranscription pathwayGene expressionJAK-STATJanus kinaseGranulocytic anaplasmosisSalivary glandsPathwayGenesCritical roleAnaplasma phagocytophilumKey role
2011
Circadian expression of clock genes in mouse macrophages, dendritic cells, and B cells
Silver AC, Arjona A, Hughes ME, Nitabach MN, Fikrig E. Circadian expression of clock genes in mouse macrophages, dendritic cells, and B cells. Brain Behavior And Immunity 2011, 26: 407-413. PMID: 22019350, PMCID: PMC3336152, DOI: 10.1016/j.bbi.2011.10.001.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsARNTL Transcription FactorsB-LymphocytesCircadian RhythmCircadian Rhythm Signaling Peptides and ProteinsCLOCK ProteinsDendritic CellsDNA-Binding ProteinsGene ExpressionMacrophagesMiceNuclear Receptor Subfamily 1, Group D, Member 1Period Circadian ProteinsPhotoperiodSpleenTranscription FactorsConceptsMolecular clock mechanismClock genesClock mechanismGene expressionClock-controlled transcription factorsFunctional molecular clockAspects of physiologyConstant environmental conditionsMolecular clockTranscription factorsCircadian expressionB cellsEnvironmental conditionsLight-dark cycleMouse macrophagesDaily rhythmsGenesExpressionCellsDendritic cellsMurine spleenMammalsMacrophagesSplenic NK cellsImmune cellsAlterations in the Aedes aegypti Transcriptome during Infection with West Nile, Dengue and Yellow Fever Viruses
Colpitts TM, Cox J, Vanlandingham DL, Feitosa FM, Cheng G, Kurscheid S, Wang P, Krishnan MN, Higgs S, Fikrig E. Alterations in the Aedes aegypti Transcriptome during Infection with West Nile, Dengue and Yellow Fever Viruses. PLOS Pathogens 2011, 7: e1002189. PMID: 21909258, PMCID: PMC3164632, DOI: 10.1371/journal.ppat.1002189.Peer-Reviewed Original ResearchConceptsGene expressionDiverse cellular processesPupal cuticle proteinsExpression of genesMosquito gene expressionYellow fever virusFlaviviral infectionsMosquito genesCuticle proteinsCellular processesBioinformatics analysisMosquito cellsExpression profilesMicroarray analysisDDR genesMetabolic processesHuman diseasesGenesTranscriptomic signaturesWest NileFever virusPeptidase activityWNV envelope proteinTranscriptomeAedes aegypti mosquitoes
2010
Anaplasma phagocytophilum induces actin phosphorylation to selectively regulate gene transcription in Ixodes scapularis ticks
Sultana H, Neelakanta G, Kantor FS, Malawista SE, Fish D, Montgomery RR, Fikrig E. Anaplasma phagocytophilum induces actin phosphorylation to selectively regulate gene transcription in Ixodes scapularis ticks. Journal Of Experimental Medicine 2010, 207: 1727-1743. PMID: 20660616, PMCID: PMC2916137, DOI: 10.1084/jem.20100276.Peer-Reviewed Original ResearchMeSH KeywordsActinsAnaplasma phagocytophilumAnimalsCell LineCell NucleusEnzyme InhibitorsGastrointestinal TractGene ExpressionGene Expression RegulationGTP-Binding Protein beta SubunitsGTP-Binding Protein gamma SubunitsInsect ProteinsIxodesP21-Activated KinasesPhosphatidylinositol 3-KinasesPhosphoinositide-3 Kinase InhibitorsPhosphorylationPromoter Regions, GeneticProtein BindingRNA InterferenceRNA Polymerase IISalivary GlandsSalivary Proteins and PeptidesSignal TransductionTATA-Box Binding ProteinTranscription, GeneticConceptsRNA polymerase IIActin phosphorylationTATA box-binding proteinNuclear G-actinPhosphorylation of actinP21-activated kinaseA. phagocytophilumA. phagocytophilum survivalTick cell linesIxodes scapularis ticksPolymerase IIPhosphorylated actinGene crucialGbetagamma subunitsGene transcriptionFilamentous actinAnaplasma phagocytophilumGene expressionBacterial acquisitionScapularis ticksPhosphorylationG-actinIntracellular pathogensMedical importanceActin
2009
Toll-Like Receptors 1 and 2 Heterodimers Alter Borrelia burgdorferi Gene Expression in Mice and Ticks
Fikrig E, Narasimhan S, Neelakanta G, Pal U, Chen M, Flavell R. Toll-Like Receptors 1 and 2 Heterodimers Alter Borrelia burgdorferi Gene Expression in Mice and Ticks. The Journal Of Infectious Diseases 2009, 200: 1331-1340. PMID: 19754309, PMCID: PMC2846271, DOI: 10.1086/605950.Peer-Reviewed Original ResearchConceptsGene expressionMicroarray analysisB. burgdorferi gene expressionQuantitative reverse transcription-polymerase chain reaction analysisToll-like receptor 1Reverse transcription-polymerase chain reaction analysisReceptor 1Expression profilesWild-type animalsHost TLRsArthropod vectorsMessenger RNA levelsPolymerase chain reaction analysisChain reaction analysisB. burgdorferi-infected ticksGenesBurgdorferi-infected ticksRNA levelsExpressionMurine hostBorrelia burgdorferiReaction analysisWild-type miceAnimalsHeterodimers
2007
Borrelia burgdorferi basic membrane proteins A and B participate in the genesis of Lyme arthritis
Pal U, Wang P, Bao F, Yang X, Samanta S, Schoen R, Wormser GP, Schwartz I, Fikrig E. Borrelia burgdorferi basic membrane proteins A and B participate in the genesis of Lyme arthritis. Journal Of Experimental Medicine 2007, 205: 133-141. PMID: 18166585, PMCID: PMC2234379, DOI: 10.1084/jem.20070962.Peer-Reviewed Original ResearchConceptsLyme arthritisMouse jointsB. burgdorferi antigensBurgdorferi-infected miceSevere arthritisSpirochete numbersArthritisHost responseLyme diseaseAffinity-purified antibodiesBorrelia burgdorferiChain reactionMiceOriginal phenotypeBasic membrane proteinMutant spirochetesGene expressionJointsInflammationPathogenesisAntigenDiseaseB. burgdorferi gene expression
2006
An Ixodes scapularis protein required for survival of Anaplasma phagocytophilum in tick salivary glands
Sukumaran B, Narasimhan S, Anderson JF, DePonte K, Marcantonio N, Krishnan MN, Fish D, Telford SR, Kantor FS, Fikrig E. An Ixodes scapularis protein required for survival of Anaplasma phagocytophilum in tick salivary glands. Journal Of Experimental Medicine 2006, 203: 1507-1517. PMID: 16717118, PMCID: PMC2118316, DOI: 10.1084/jem.20060208.Peer-Reviewed Original ResearchConceptsA. phagocytophilum-infected miceRNA interference-mediated silencingA. phagocytophilumTick salivary proteinsI. scapularis salivary glandsRickettsia-like pathogensTick salivary glandsMammalian hostsGenus RickettsiaAnaplasma phagocytophilumGene expressionSalivary glandsIntracellular organismsArthropodsSalivary proteinsPathogensProteinPhagocytophilumExpressionTicksHuman anaplasmosisSilencingGenesOrganismsAnaplasmaMechanisms of evasion of neutrophil killing by Anaplasma phagocytophilum
Carlyon JA, Fikrig E. Mechanisms of evasion of neutrophil killing by Anaplasma phagocytophilum. Current Opinion In Hematology 2006, 13: 28-33. PMID: 16319684, DOI: 10.1097/01.moh.0000190109.00532.56.Peer-Reviewed Original ResearchConceptsApoptosis differentiation programMitochondrial membrane integrityA. phagocytophilumCaspase-3 activationBacterium altersMolecular machineryVacuolar membraneTranscription factorsDifferentiation programMammalian hostsSecretory vesiclesAnaplasma phagocytophilumCytoplasmic compartmentGene expressionPromoter activityAntiapoptotic genesNADPH oxidase assemblyOxidase assemblyNeutrophil gene expressionHost cellsBacterial uptakeNADPH oxidase componentsMechanisms of evasionMembrane integrityCytochrome b558
2005
Early Transcriptional Response of Human Neutrophils to Anaplasma phagocytophilum Infection
Sukumaran B, Carlyon JA, Cai JL, Berliner N, Fikrig E. Early Transcriptional Response of Human Neutrophils to Anaplasma phagocytophilum Infection. Infection And Immunity 2005, 73: 8089-8099. PMID: 16299303, PMCID: PMC1307096, DOI: 10.1128/iai.73.12.8089-8099.2005.Peer-Reviewed Original ResearchConceptsEarly transcriptional responseTranscriptional responseGene expressionHost cell gene expressionComprehensive DNA microarray analysisA. phagocytophilum infectionDNA microarray analysisObligate intracellular pathogensCell gene expressionCFLAR geneTNFSF10 geneA. phagocytophilum-infected neutrophilsCytoskeletal remodelingVesicular transportTranscriptional profilesHost pathwaysMicroarray analysisAntiapoptotic genesPromyelocytic cell lineDifferential expressionPhagocytophilum infectionHost cellsGenesHuman neutrophilsIntracellular pathogensAnaplasma phagocytophilum Modulates gp91phox Gene Expression through Altered Interferon Regulatory Factor 1 and PU.1 Levels and Binding of CCAAT Displacement Protein
Thomas V, Samanta S, Wu C, Berliner N, Fikrig E. Anaplasma phagocytophilum Modulates gp91phox Gene Expression through Altered Interferon Regulatory Factor 1 and PU.1 Levels and Binding of CCAAT Displacement Protein. Infection And Immunity 2005, 73: 208-218. PMID: 15618156, PMCID: PMC538944, DOI: 10.1128/iai.73.1.208-218.2005.Peer-Reviewed Original ResearchMeSH KeywordsAnaplasma phagocytophilumDNA-Binding ProteinsGene Expression RegulationHL-60 CellsHomeodomain ProteinsHumansInterferon Regulatory Factor-1Membrane GlycoproteinsNADPH Oxidase 2NADPH OxidasesNuclear ProteinsPhosphoproteinsPhosphorylationPromoter Regions, GeneticProto-Oncogene ProteinsRepressor ProteinsSTAT1 Transcription FactorTrans-ActivatorsTranscription FactorsTranscription, GeneticConceptsCCAAT displacement proteinRegulatory factor 1IRF-1IRF-1 promoterRegulation of genesA. phagocytophilum-infected cellsFirst molecular mechanismFactor 1Interferon regulatory factor 1IFN-gamma signalingActivator proteinGene transcriptionAnaplasma phagocytophilumTranscriptional inhibitionGene expressionMolecular mechanismsNuclear extractsGamma interferon stimulationPhosphorylated STAT1Interferon stimulationGenesA. phagocytophilum infectionProteinProtein expressionReduced expression
2004
OspC facilitates Borrelia burgdorferi invasion of Ixodes scapularis salivary glands
Pal U, Yang X, Chen M, Bockenstedt LK, Anderson JF, Flavell RA, Norgard MV, Fikrig E. OspC facilitates Borrelia burgdorferi invasion of Ixodes scapularis salivary glands. Journal Of Clinical Investigation 2004, 113: 220-230. PMID: 14722614, PMCID: PMC311436, DOI: 10.1172/jci19894.Peer-Reviewed Original ResearchMeSH KeywordsActinsAnimalsAntigens, BacterialBacterial Outer Membrane ProteinsBorrelia burgdorferiDisease Models, AnimalEnzyme-Linked Immunosorbent AssayGenetic VectorsImmunoglobulin Fab FragmentsIxodesLipoproteinsLyme DiseaseMiceMice, SCIDMicroscopy, ConfocalModels, GeneticPlasmidsRecombinant ProteinsReverse Transcriptase Polymerase Chain ReactionSalivary GlandsSpirochaetalesTime FactorsUp-RegulationConceptsTick salivary glandsWild-type B. burgdorferiArthropod vectorsWild-type spirochetesTransmission of spirochetesB. burgdorferiMajor surface lipoproteinMammalian hostsGene expressionSalivary glandsOspC geneSurface lipoproteinsSalivary gland colonizationInfectious cloneOuter surface protein CGland colonizationSurface protein CTick gutMutantsOspCUnfed ticksInvasionCritical stepBorrelia burgdorferiSpirochetes
2003
Borrelia burgdorferi transcriptome in the central nervous system of non-human primates
Narasimhan S, Camaino M, Liang FT, Santiago F, Laskowski M, Philipp MT, Pachner AR, Radolf JD, Fikrig E. Borrelia burgdorferi transcriptome in the central nervous system of non-human primates. Proceedings Of The National Academy Of Sciences Of The United States Of America 2003, 100: 15953-15958. PMID: 14671329, PMCID: PMC307674, DOI: 10.1073/pnas.2432412100.Peer-Reviewed Original ResearchConceptsNon-human primate modelB. burgdorferiEffect of dexamethasoneCentral nervous systemHost metabolic pathwaysNon-human primatesNeurological symptomsPaucibacillary natureCNS milieuImmune statusCommon manifestationPrimate modelNervous systemExpression profilesLyme diseaseHost factorsHeart tissueGene expressionB. burgdorferi transcriptomeBorrelia burgdorferiNHPNeuroborreliosisImmunocompetentVivo gene expressionBurgdorferiAdaptation of Borrelia burgdorferi in the tick and the mammalian host
Anguita J, Hedrick MN, Fikrig E. Adaptation of Borrelia burgdorferi in the tick and the mammalian host. FEMS Microbiology Reviews 2003, 27: 493-504. PMID: 14550942, DOI: 10.1016/s0168-6445(03)00036-6.Peer-Reviewed Original ResearchConceptsMammalian hostsGene expressionRegulation of genesAdaptation of BorreliaGene productsDifferent environmentsArthropod vectorsEnzootic cycleCurrent knowledgeLife cycleHostExpressionCausative agentB. burgdorferiBorrelia burgdorferiGenesSpirochetesTicksBurgdorferiMicroorganismsGreater abilityRegulationLyme diseaseThorough understandingFunction
2002
Examination of the Borrelia burgdorferi Transcriptome in Ixodes scapularis during Feeding
Narasimhan S, Santiago F, Koski RA, Brei B, Anderson JF, Fish D, Fikrig E. Examination of the Borrelia burgdorferi Transcriptome in Ixodes scapularis during Feeding. Journal Of Bacteriology 2002, 184: 3122-3125. PMID: 12003955, PMCID: PMC135063, DOI: 10.1128/jb.184.11.3122-3125.2002.Peer-Reviewed Original ResearchConceptsBorrelia burgdorferi gene expressionB. burgdorferi genesPeriplasmic proteinsSignal transductionChromosomal genesPutative lipoproteinSubstrate transportGene expressionDifferential expressionGenesEnergy metabolismIxodes scapularis ticksGlobal analysisIxodes scapularisScapularis ticksExpressionTranscriptomeTransductionTicksProteinFeedingMetabolismScapularis