2020
An Ixodes scapularis Protein Disulfide Isomerase Contributes to Borrelia burgdorferi Colonization of the Vector
Cao Y, Rosen C, Arora G, Gupta A, Booth CJ, Murfin KE, Cerny J, Lopez A, Chuang YM, Tang X, Pal U, Ring A, Narasimhan S, Fikrig E. An Ixodes scapularis Protein Disulfide Isomerase Contributes to Borrelia burgdorferi Colonization of the Vector. Infection And Immunity 2020, 88: 10.1128/iai.00426-20. PMID: 32928964, PMCID: PMC7671890, DOI: 10.1128/iai.00426-20.Peer-Reviewed Original ResearchConceptsTick gutTick bite siteVector-host interfaceAbility of spirochetesProtein disulfide isomerase A3Infected vertebrate hostsInflammatory responseBite siteLyme diseaseVertebrate hostsGutTick proteinsAdditional targetsMiceSpirochete life cycleSpirochete survivalArthropod vectorsSpirochetesRNA interferenceIllnessTicks
2019
Aedes aegypti AgBR1 antibodies modulate early Zika virus infection of mice
Uraki R, Hastings AK, Marin-Lopez A, Sumida T, Takahashi T, Grover JR, Iwasaki A, Hafler DA, Montgomery RR, Fikrig E. Aedes aegypti AgBR1 antibodies modulate early Zika virus infection of mice. Nature Microbiology 2019, 4: 948-955. PMID: 30858571, PMCID: PMC6533137, DOI: 10.1038/s41564-019-0385-x.Peer-Reviewed Original ResearchConceptsZika virus infectionVirus infectionZika virusAegypti salivary proteinsGuillain-Barre syndromeEarly inflammatory responseSkin of micePrevention of mosquitoInflammatory responseAedes aegypti mosquitoesTherapeutic measuresSalivary factorsSalivary proteinsMosquito-borneInfectionMiceSubstantial mortalityRecent epidemicProtein 1Aegypti mosquitoesAntigenic proteinsVirusAntibodiesMosquitoesAntiserum
2017
Advances in Serodiagnostic Testing for Lyme Disease Are at Hand
Branda JA, Body BA, Boyle J, Branson BM, Dattwyler RJ, Fikrig E, Gerald NJ, Gomes-Solecki M, Kintrup M, Ledizet M, Levin AE, Lewinski M, Liotta LA, Marques A, Mead PS, Mongodin EF, Pillai S, Rao P, Robinson WH, Roth KM, Schriefer ME, Slezak T, Snyder J, Steere AC, Witkowski J, Wong SJ, Schutzer SE. Advances in Serodiagnostic Testing for Lyme Disease Are at Hand. Clinical Infectious Diseases 2017, 66: 1133-1139. PMID: 29228208, PMCID: PMC6019075, DOI: 10.1093/cid/cix943.Peer-Reviewed Original ResearchConceptsSerodiagnostic testingEnzyme immunoassayLyme diseaseIndirect fluorescence antibodySerologic assaysImmunoglobulin MEarly infectionFluorescence antibodyTesting protocolAlternative testing protocolsBorrelia burgdorferiB. burgdorferiWestern immunoblotAntigenDiseaseAntibodiesBurgdorferiLow sensitivitySynthetic peptidesAssaysInfection-derived lipids elicit an immune deficiency circuit in arthropods
Shaw DK, Wang X, Brown LJ, Chávez AS, Reif KE, Smith AA, Scott AJ, McClure EE, Boradia VM, Hammond HL, Sundberg EJ, Snyder GA, Liu L, DePonte K, Villar M, Ueti MW, de la Fuente J, Ernst RK, Pal U, Fikrig E, Pedra JH. Infection-derived lipids elicit an immune deficiency circuit in arthropods. Nature Communications 2017, 8: 14401. PMID: 28195158, PMCID: PMC5316886, DOI: 10.1038/ncomms14401.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAnaplasma marginaleAnaplasma phagocytophilumAnimalsArthropodsBorrelia burgdorferiCarrier ProteinsDisease Models, AnimalDrosophila melanogasterDrosophila ProteinsEscherichia coliFas-Associated Death Domain ProteinGene SilencingHEK293 CellsHumansImmunologic Deficiency SyndromesIxodesLipidsLyme DiseasePhosphatidylglycerolsRecombinant ProteinsRNA, Small InterferingSignal TransductionTranscription FactorsUbiquitin-Conjugating EnzymesUbiquitin-Protein LigasesX-Linked Inhibitor of Apoptosis ProteinConceptsAdaptor molecule FasImmune deficiency (IMD) pathwayPeptidoglycan recognition proteinsE3 ubiquitin ligaseLyme disease spirochete Borrelia burgdorferiIMD pathwayGram-negative bacteriaRecognition proteinsUbiquitin ligaseDeath domainApoptosis proteinDistinct bacteriaBiochemical interactionsMolecule FasSpirochete Borrelia burgdorferiReceptor networkA. marginaleProteinAnaplasma phagocytophilumBacteriaPathwayBorrelia burgdorferiInsectsLipidsArthropods
2016
Interleukin-17A Promotes CD8+ T Cell Cytotoxicity To Facilitate West Nile Virus Clearance
Acharya D, Wang P, Paul AM, Dai J, Gate D, Lowery JE, Stokic DS, Leis AA, Flavell RA, Town T, Fikrig E, Bai F. Interleukin-17A Promotes CD8+ T Cell Cytotoxicity To Facilitate West Nile Virus Clearance. Journal Of Virology 2016, 91: 10.1128/jvi.01529-16. PMID: 27795421, PMCID: PMC5165211, DOI: 10.1128/jvi.01529-16.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBrainCytotoxicity, ImmunologicFemaleGene ExpressionHumansInterleukin-17MiceMice, Inbred C57BLNeuronsPrimary Cell CultureReceptors, Interleukin-17Recombinant ProteinsSurvival AnalysisT-Lymphocytes, CytotoxicTreatment OutcomeViral LoadVirus ReplicationWest Nile FeverWest Nile virusConceptsT cell cytotoxicityRecombinant IL-17AWest Nile virus infectionWNV-infected miceIL-17AT cellsViral burdenWNV infectionCell cytotoxicityInterleukin-17AVirus infectionMicrobial infectionsIL-17A-deficient miceT cell-mediated clearanceHigh viral burdenT-cell axisLethal WNV infectionSurvival of miceDay 6 postinfectionT cell functionWild-type miceDiverse immune functionsIL-17A.Proinflammatory cytokinesAutoimmune diseases
2015
Ixodes scapularis dystroglycan-like protein promotes Borrelia burgdorferi migration from the gut
Coumou J, Narasimhan S, Trentelman JJ, Wagemakers A, Koetsveld J, Ersoz JI, Oei A, Fikrig E, Hovius JW. Ixodes scapularis dystroglycan-like protein promotes Borrelia burgdorferi migration from the gut. Journal Of Molecular Medicine 2015, 94: 361-370. PMID: 26594018, PMCID: PMC4803822, DOI: 10.1007/s00109-015-1365-0.Peer-Reviewed Original ResearchConceptsB. burgdorferi transmissionTick gutLyme borreliosisTick feedingMurine modelVaccine targetsUninfected ticksRNA interferenceInfected ticksSalivary glandsBorrelia burgdorferiPotential targetGut tissueB. burgdorferiCausative agentIxodes ticksGutPrevious screeningTick proteinsGut cellsBurgdorferiMiceTicks resultsBorreliosisConfocal microscopy
2014
Antivirulence Properties of an Antifreeze Protein
Heisig M, Abraham NM, Liu L, Neelakanta G, Mattessich S, Sultana H, Shang Z, Ansari JM, Killiam C, Walker W, Cooley L, Flavell RA, Agaisse H, Fikrig E. Antivirulence Properties of an Antifreeze Protein. Cell Reports 2014, 9: 417-424. PMID: 25373896, PMCID: PMC4223805, DOI: 10.1016/j.celrep.2014.09.034.Peer-Reviewed Original ResearchConceptsAntifreeze proteinsDiverse bacteriaProtein bindsWild-type animalsBiofilm formationAntivirulence agentsIAFGPMethicillin-resistant Staphylococcus aureusHost controlProteinAntifreeze glycoproteinsIxodes scapularisAntivirulence propertiesBacteriaSeptic shockTherapeutic strategiesBacterial infectionsInfectious diseasesMicrobesStaphylococcus aureusFliesBindsInfectionCatheter tubingPathogens
2013
Characterization of Ixophilin, A Thrombin Inhibitor from the Gut of Ixodes scapularis
Narasimhan S, Perez O, Mootien S, DePonte K, Koski RA, Fikrig E, Ledizet M. Characterization of Ixophilin, A Thrombin Inhibitor from the Gut of Ixodes scapularis. PLOS ONE 2013, 8: e68012. PMID: 23874485, PMCID: PMC3706618, DOI: 10.1371/journal.pone.0068012.Peer-Reviewed Original ResearchConceptsTick gutBlood mealVertebrate hostsTick gut proteinsPathogen transmissionBorrelia burgdorferi transmissionAnticoagulation strategiesThrombin inhibitory activityHemostatic mechanismThrombin inhibitorsMammalian coagulationIxodes scapularisMammalian hostsTick salivaLyme diseaseKey enzymeGut proteinsBorrelia burgdorferiTick feedingHost bloodHours of feedingGutFunctional suiteTick proteinsHuman pathogensFactor Xa Activation of Factor V Is of Paramount Importance in Initiating the Coagulation System
Schuijt TJ, Bakhtiari K, Daffre S, DePonte K, Wielders SJ, Marquart JA, Hovius JW, van der Poll T, Fikrig E, Bunce MW, Camire RM, Nicolaes GA, Meijers JC, van ‘t Veer C. Factor Xa Activation of Factor V Is of Paramount Importance in Initiating the Coagulation System. Circulation 2013, 128: 254-266. PMID: 23817575, PMCID: PMC3826089, DOI: 10.1161/circulationaha.113.003191.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAnticoagulantsArthropod ProteinsBlood CoagulationBlood Coagulation TestsDose-Response Relationship, DrugFactor VFactor XaFactor Xa InhibitorsFeeding BehaviorFibrinogenHumansIxodesMutagenesisProtein Structure, TertiaryRabbitsRecombinant ProteinsSalivary Proteins and PeptidesSurface Plasmon ResonanceThrombin
2012
SERUM ANTIBODIES TO WHOLE-CELL AND RECOMBINANT ANTIGENS OF BORRELIA BURGDORFERI IN COTTONTAIL RABBITS
Magnarelli LA, Norris SJ, Fikrig E. SERUM ANTIBODIES TO WHOLE-CELL AND RECOMBINANT ANTIGENS OF BORRELIA BURGDORFERI IN COTTONTAIL RABBITS. Journal Of Wildlife Diseases 2012, 48: 12-20. PMID: 22247369, PMCID: PMC3261588, DOI: 10.7589/0090-3558-48.1.12.Peer-Reviewed Original Research
2011
Humoral immune responses in humanized BLT mice immunized with West Nile virus and HIV‐1 envelope proteins are largely mediated via human CD5+ B cells
Biswas S, Chang H, Sarkis PT, Fikrig E, Zhu Q, Marasco WA. Humoral immune responses in humanized BLT mice immunized with West Nile virus and HIV‐1 envelope proteins are largely mediated via human CD5+ B cells. Immunology 2011, 134: 419-433. PMID: 22044090, PMCID: PMC3230796, DOI: 10.1111/j.1365-2567.2011.03501.x.Peer-Reviewed Original ResearchConceptsHumoral immune responseImmune responseBLT miceB cellsB lymphocytesVaccine-induced humoral immune responsesVaccine-induced immune responsesVaccine-induced antibody responsesNon-obese diabetic/T cell-independent pathwayHIV-1 envelope proteinSecondary immune responseSingle intramuscular immunizationSpecific IgM levelsViral envelope antigensB cell subsetsAntigen-specific human antibodiesFollicular B cellsCytokines/growth factorsEnvelope proteinHuman B lymphocytesHuman lymphoid systemMature follicular B cellsWest Nile virus envelope proteinHuman T lymphocytesA Tick Mannose-Binding Lectin Inhibitor Interferes with the Vertebrate Complement Cascade to Enhance Transmission of the Lyme Disease Agent
Schuijt TJ, Coumou J, Narasimhan S, Dai J, DePonte K, Wouters D, Brouwer M, Oei A, Roelofs JJ, van Dam AP, van der Poll T, Veer C, Hovius JW, Fikrig E. A Tick Mannose-Binding Lectin Inhibitor Interferes with the Vertebrate Complement Cascade to Enhance Transmission of the Lyme Disease Agent. Cell Host & Microbe 2011, 10: 136-146. PMID: 21843870, PMCID: PMC3170916, DOI: 10.1016/j.chom.2011.06.010.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsBorrelia burgdorferiCell Migration AssaysCloning, MolecularComplement Membrane Attack ComplexComplement Pathway, Mannose-Binding LectinFemaleGene SilencingHemolysisHumansImmunization, PassiveImmunotherapy, ActiveInsect ProteinsIxodesLarvaLyme DiseaseMiceMice, Inbred C3HMolecular Sequence DataNeutrophilsNymphPhagocytosisRabbitsRecombinant ProteinsSalivaSalivary Proteins and PeptidesSequence AlignmentConceptsComplement cascadeLyme disease agent Borrelia burgdorferiImpaired neutrophil phagocytosisTick salivary proteinsVector-borne pathogensLyme disease agentMammalian infectionVector colonizationVertebrate hostsTick midgutAlternative complement pathwayBorrelia transmissionComplement-mediated killingVector proteinNeutrophil phagocytosisEssential rolePathway inhibitorComplement pathwayDisease agentsSalivary proteinsBorrelia burgdorferiLectin inhibitorsProteinCascadeIxodes ticks
2008
A recombinant West Nile virus envelope protein vaccine candidate produced in Spodoptera frugiperda expresSF+ cells
Bonafé N, Rininger JA, Chubet RG, Foellmer HG, Fader S, Anderson JF, Bushmich SL, Anthony K, Ledizet M, Fikrig E, Koski RA, Kaplan P. A recombinant West Nile virus envelope protein vaccine candidate produced in Spodoptera frugiperda expresSF+ cells. Vaccine 2008, 27: 213-222. PMID: 18996430, PMCID: PMC2651515, DOI: 10.1016/j.vaccine.2008.10.046.Peer-Reviewed Original ResearchConceptsVaccine candidatesClinical adverse effectsProtein vaccine candidateRecombinant vaccine candidateWNV vaccineAntibody titersHumoral immunityProtective efficacySafe vaccineWNV infectionChallenge modelVaccine antigensAnimal modelsViral protectionHigh dosesProtein antigensAdverse effectsImmunogenicitySerum-free cultureAntigenCell linesNaïve foalsVaccineAluminum hydroxideInfectionSalp15 Binding to DC-SIGN Inhibits Cytokine Expression by Impairing both Nucleosome Remodeling and mRNA Stabilization
Hovius JW, de Jong MA, Dunnen J, Litjens M, Fikrig E, van der Poll T, Gringhuis SI, Geijtenbeek TB. Salp15 Binding to DC-SIGN Inhibits Cytokine Expression by Impairing both Nucleosome Remodeling and mRNA Stabilization. PLOS Pathogens 2008, 4: e31. PMID: 18282094, PMCID: PMC2242833, DOI: 10.1371/journal.ppat.0040031.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBorrelia burgdorferiCell Adhesion MoleculesCells, CulturedCytokinesDendritic CellsDose-Response Relationship, DrugHumansIxodesLectins, C-TypeNucleosomesProtein BindingProto-Oncogene Proteins c-rafReceptors, Cell SurfaceRecombinant ProteinsRNA, MessengerSalivary Proteins and PeptidesToll-Like ReceptorsConceptsRaf-1B. burgdorferi infectionSerine/threonine kinase Raf-1Mitogen-activated protein kinase kinaseKinase Raf-1Post-transcriptional levelLyme diseaseProtein kinase kinaseRaf-1 activationBurgdorferi infectionDC-SIGNTNF-alpha mRNA stabilityHuman dendritic cell functionNucleosome remodelingTick salivary proteinsDendritic cell functionKinase kinasePro-inflammatory cytokinesAdaptive immune responsesToll-like receptorsMRNA stabilityMRNA stabilizationT cell activationMolecular mechanismsMajor vector
2007
West Nile Virus Envelope Protein Inhibits dsRNA-Induced Innate Immune Responses
Arjona A, Ledizet M, Anthony K, Bonafé N, Modis Y, Town T, Fikrig E. West Nile Virus Envelope Protein Inhibits dsRNA-Induced Innate Immune Responses. The Journal Of Immunology 2007, 179: 8403-8409. PMID: 18056386, DOI: 10.4049/jimmunol.179.12.8403.Peer-Reviewed Original ResearchConceptsWest Nile virusInnate immune responseReceptor-interacting protein 1Immune responseMajor structural proteinVirus-associated molecular patternsDipteran cellsViral replication intermediatesRNA helicasesAdaptor molecule TRIFReplication intermediatesStructural proteinsWNV envelope proteinGlycosylation patternsMolecular patternsAntiviral stateGlycosylation profileProtein 1Murine macrophagesProinflammatory cytokinesCytokine productionImmunosuppressive effectsDsRNAImmune cellsEnvelope protein
2006
The Lyme disease agent Borrelia burgdorferi requires BB0690, a Dps homologue, to persist within ticks
Li X, Pal U, Ramamoorthi N, Liu X, Desrosiers DC, Eggers CH, Anderson JF, Radolf JD, Fikrig E. The Lyme disease agent Borrelia burgdorferi requires BB0690, a Dps homologue, to persist within ticks. Molecular Microbiology 2006, 63: 694-710. PMID: 17181780, DOI: 10.1111/j.1365-2958.2006.05550.x.Peer-Reviewed Original Research
2005
Detection of antibodies to Borrelia burgdorferi in naturally infected horses in the USA by enzyme-linked immunosorbent assay using whole-cell and recombinant antigens
Magnarelli L, Fikrig E. Detection of antibodies to Borrelia burgdorferi in naturally infected horses in the USA by enzyme-linked immunosorbent assay using whole-cell and recombinant antigens. Research In Veterinary Science 2005, 79: 99-103. PMID: 15924926, DOI: 10.1016/j.rvsc.2004.11.009.Peer-Reviewed Original Research
2004
TROSPA, an Ixodes scapularis Receptor for Borrelia burgdorferi
Pal U, Li X, Wang T, Montgomery RR, Ramamoorthi N, deSilva AM, Bao F, Yang X, Pypaert M, Pradhan D, Kantor FS, Telford S, Anderson JF, Fikrig E. TROSPA, an Ixodes scapularis Receptor for Borrelia burgdorferi. Cell 2004, 119: 457-468. PMID: 15537536, DOI: 10.1016/j.cell.2004.10.027.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsAntibodies, BacterialAntigens, SurfaceBacterial Outer Membrane ProteinsBacterial VaccinesBase SequenceBorrelia burgdorferiCloning, MolecularGene Expression RegulationHost-Parasite InteractionsIntestinesIxodesLipoproteinsMiceMice, Inbred C3HMolecular Sequence DataReceptors, Cell SurfaceRecombinant ProteinsConceptsLyme disease agent Borrelia burgdorferiSurvival of spirochetesTick receptorMammalian hostsRNA interferenceEfficient colonizationTROSPAOuter surface protein ABorrelia burgdorferiPathogen adherencePathogen transmissionProtein AB. burgdorferi outer surface protein AMRNA levelsIxodes scapularisB. burgdorferiColonizationSurface protein AReceptorsArthropodsBurgdorferiMammalsRepressionSpirochetesTicksA comparison of serologic tests for the detection of serum antibodies to whole-cell and recombinant Borrelia burgdorferi antigens in cattle.
Magnarelli LA, Bushmich SL, Sherman BA, Fikrig E. A comparison of serologic tests for the detection of serum antibodies to whole-cell and recombinant Borrelia burgdorferi antigens in cattle. Canadian Veterinary Journal 2004, 45: 667-73. PMID: 15368740, PMCID: PMC546445.Peer-Reviewed Original ResearchMeSH KeywordsAnaplasma phagocytophilumAnimalsAntibodies, BacterialAntigens, BacterialBlotting, WesternBorrelia burgdorferiCattleCattle DiseasesConnecticutEnzyme-Linked Immunosorbent AssayFemaleFluorescent Antibody Technique, IndirectLyme DiseaseMaleMolecular WeightRecombinant ProteinsReproducibility of ResultsSensitivity and SpecificityTick InfestationsConceptsPolyvalent enzyme-linked immunosorbentVlsE antigenBorrelia burgdorferi antigensRecombinant antigensAntibody staining methodsHealthy dairyB. burgdorferi antigensIndirect fluorescent-antibody staining methodsCattle seraHigh specificityLeptospira interrogans serovarsBrucella spWhole cell antigenSerum samplesWestern blot procedureP39 antigenUSE OF RECOMBINANT ANTIGENS OF BORRELIA BURGDORFERI AND ANAPLASMA PHAGOCYTOPHILUM IN ENZYME-LINKED IMMUNOSORBENT ASSAYS TO DETECT ANTIBODIES IN WHITE-TAILED DEER
Magnarelli LA, IJdo JW, Ramakrishnan U, Henderson DW, Stafford KC, Fikrig E. USE OF RECOMBINANT ANTIGENS OF BORRELIA BURGDORFERI AND ANAPLASMA PHAGOCYTOPHILUM IN ENZYME-LINKED IMMUNOSORBENT ASSAYS TO DETECT ANTIBODIES IN WHITE-TAILED DEER. Journal Of Wildlife Diseases 2004, 40: 249-258. PMID: 15362824, DOI: 10.7589/0090-3558-40.2.249.Peer-Reviewed Original Research