2021
A Mosquito AgTRIO Monoclonal Antibody Reduces Early Plasmodium Infection of Mice
Chuang YM, Tang XD, Fikrig E. A Mosquito AgTRIO Monoclonal Antibody Reduces Early Plasmodium Infection of Mice. Infection And Immunity 2021, 90: e00359-21. PMID: 34724388, PMCID: PMC8788779, DOI: 10.1128/iai.00359-21.Peer-Reviewed Original ResearchConceptsMonoclonal antibodiesFuture malaria vaccinesInfection of miceIsotype monoclonal antibodyVector antigensProtective immunityPassive immunizationMalaria vaccinePlasmodium infectionPassive transferProtein monoclonal antibodySignificant protectionSynergistic protectionMiceInfectionAntibodiesFc regionAntiserumVertebrate hostsProtein TrioImmunizationVaccineMalariaAntigenImmunity
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
2016
Variable Major Proteins as Targets for Specific Antibodies against Borrelia miyamotoi
Wagemakers A, Koetsveld J, Narasimhan S, Wickel M, Deponte K, Bleijlevens B, Jahfari S, Sprong H, Karan LS, Sarksyan DS, van der Poll T, Bockenstedt LK, Bins AD, Platonov AE, Fikrig E, Hovius JW. Variable Major Proteins as Targets for Specific Antibodies against Borrelia miyamotoi. The Journal Of Immunology 2016, 196: 4185-4195. PMID: 27076681, PMCID: PMC5008243, DOI: 10.4049/jimmunol.1600014.Peer-Reviewed Original ResearchConceptsVariable major proteinsB. miyamotoiSerologic testsC3H/HeN miceBorrelia miyamotoiHumoral immune responseInfected SCID miceTick-borne relapsing feverIgM reactivityHumoral immunityHeN miceIgM productionPassive transferSCID miceSerologic assaysCurrent serologic assaysImmune responseImmune serumRelapsing feverSpecific antibodiesProtein 1MiyamotoiIxodes ticksPatientsFever spirochetes
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 pathogens
2012
Anaplasma phagocytophilum Asp14 Is an Invasin That Interacts with Mammalian Host Cells via Its C Terminus To Facilitate Infection
Kahlon A, Ojogun N, Ragland SA, Seidman D, Troese MJ, Ottens AK, Mastronunzio JE, Truchan HK, Walker NJ, Borjesson DL, Fikrig E, Carlyon JA. Anaplasma phagocytophilum Asp14 Is an Invasin That Interacts with Mammalian Host Cells via Its C Terminus To Facilitate Infection. Infection And Immunity 2012, 81: 65-79. PMID: 23071137, PMCID: PMC3536139, DOI: 10.1128/iai.00932-12.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnaplasma phagocytophilumAnimalsBacterial Outer Membrane ProteinsBinding SitesCell AdhesionCell Line, TumorEhrlichiaEhrlichiosisGene Expression Regulation, BacterialGlutathione TransferaseHL-60 CellsHumansMembrane GlycoproteinsMembrane ProteinsMiceMolecular Sequence DataProtein BindingProtein Structure, TertiaryProteomeSequence Analysis, ProteinTranscription, GeneticUp-RegulationConceptsMammalian host cellsHost cellsReticulate cellsOuter membrane protein candidatesSurface proteinsOuter membrane protein AMembrane protein AA. phagocytophilum-infected ticksObligate intracellular bacteriumA. phagocytophilumGlutathione S-transferaseTranscriptional profilingSurface proteomeC-terminusAffinity purificationFamily AnaplasmataceaeProtein candidatesSelective biotinylationCellular invasionAsp14Transmission feedingAmino acidsS-transferaseIntracellular bacteriumP-selectin glycoprotein ligand-1
2011
A 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
2010
Fucosylation enhances colonization of ticks by Anaplasma phagocytophilum
Pedra JH, Narasimhan S, Rendić D, DePonte K, Bell‐Sakyi L, Wilson IB, Fikrig E. Fucosylation enhances colonization of ticks by Anaplasma phagocytophilum. Cellular Microbiology 2010, 12: 1222-1234. PMID: 20331643, PMCID: PMC3250644, DOI: 10.1111/j.1462-5822.2010.01464.x.Peer-Reviewed Original ResearchConceptsA. phagocytophilumAnaplasma phagocytophilumHuman granulocytic anaplasmosisBacterium Anaplasma phagocytophilumGranulocytic anaplasmosisPathological processesTick feedingPhagocytophilumMicrobial pathogenesisNovel mechanismPathogen colonizationTick cellsFucosylated structuresTicksPathogen invasionPathogenesis
2007
Antibodies Targeting Linear Determinants of the Envelope Protein Protect Mice against West Nile Virus
Ledizet M, Kar K, Foellmer HG, Bonafé N, Anthony KG, Gould LH, Bushmich SL, Fikrig E, Koski RA. Antibodies Targeting Linear Determinants of the Envelope Protein Protect Mice against West Nile Virus. The Journal Of Infectious Diseases 2007, 196: 1741-1748. PMID: 18190253, DOI: 10.1086/523654.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsAntibodies, ViralAntibody AffinityChlorocebus aethiopsDrosophilaEpitopesFemaleFluorescent Antibody TechniqueHorsesImmunization, PassiveImmunoglobulinsMiceMice, Inbred C3HMolecular Sequence DataPeptide FragmentsVero CellsViral Envelope ProteinsWest Nile FeverWest Nile virusConceptsE proteinMultiple flavivirus infectionsVirus-neutralizing antibodiesE protein epitopesFlavivirus envelope proteinProtect miceWest Nile virusFlavivirus infectionLethal challengeProtective antibodiesWest Nile virus E proteinProtective epitopesVirus E proteinRelated flavivirusesImmunoglobulinAntibodiesNile virusLinear determinantsEpitopesEnvelope proteinProtein epitopesMiceHost cell membraneWNVPeptidesIdentification of Salp15 Homologues in Ixodes ricinus Ticks
Hovius JW, Ramamoorthi N, Veer C, de Groot KA, Nijhof AM, Jongejan F, van Dam AP, Fikrig E. Identification of Salp15 Homologues in Ixodes ricinus Ticks. Vector-Borne And Zoonotic Diseases 2007, 7: 296-303. PMID: 17896872, DOI: 10.1089/vbz.2006.0624.Peer-Reviewed Original ResearchConceptsSalp15 homologuesI. scapularis Salp15T cell activationDifferent Ixodes speciesAmino acid sequenceEntire amino acid sequenceSignal sequenceMammalian hostsProtein sequencesAcid sequenceC-terminusReverse transcriptase-polymerase chain reactionSensu strictoIxodes speciesSensu latoMajor vectorHomologuesB. burgdorferi sensu latoBorrelia speciesProteinSalp15Borrelia burgdorferi sensu strictoSpeciesI. ricinusBurgdorferi sensu strictoBiochemical and Functional Characterization of Salp20, an Ixodes scapularis Tick Salivary Protein that Inhibits the Complement Pathway
Tyson K, Elkins C, Patterson H, Fikrig E, De Silva A. Biochemical and Functional Characterization of Salp20, an Ixodes scapularis Tick Salivary Protein that Inhibits the Complement Pathway. Insect Molecular Biology 2007, 16: 469-479. PMID: 17651236, DOI: 10.1111/j.1365-2583.2007.00742.x.Peer-Reviewed Original Research
2006
Antiviral Peptides Targeting the West Nile Virus Envelope Protein
Bai F, Town T, Pradhan D, Cox J, Ashish, Ledizet M, Anderson JF, Flavell RA, Krueger JK, Koski RA, Fikrig E. Antiviral Peptides Targeting the West Nile Virus Envelope Protein. Journal Of Virology 2006, 81: 2047-2055. PMID: 17151121, PMCID: PMC1797586, DOI: 10.1128/jvi.01840-06.Peer-Reviewed Original ResearchConceptsWest Nile virusMurine blood-brain barrierEnvelope proteinBlood-brain barrierPeptide 9West Nile encephalitisWNV envelope proteinCentral nervous systemWest Nile virus envelope proteinCDNA phage display libraryBrain parenchymaVirus envelope proteinHuman encephalitisViral envelope proteinsWNV infectionControl animalsPeptide-1Nervous systemRelated flavivirusesDengue virusAntiviral activityNew therapeuticsInhibition concentrationAntiviral peptidesNile virusThe 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 ResearchCrystal Structure of West Nile Virus Envelope Glycoprotein Reveals Viral Surface Epitopes
Kanai R, Kar K, Anthony K, Gould LH, Ledizet M, Fikrig E, Marasco WA, Koski RA, Modis Y. Crystal Structure of West Nile Virus Envelope Glycoprotein Reveals Viral Surface Epitopes. Journal Of Virology 2006, 80: 11000-11008. PMID: 16943291, PMCID: PMC1642136, DOI: 10.1128/jvi.01735-06.Peer-Reviewed Original ResearchConceptsWest Nile virus-specific antibodiesEnvelope glycoproteinTick-borne encephalitis virusWest Nile Virus Envelope GlycoproteinLife-threatening encephalitisVirus-specific antibodiesWest Nile virusMajor envelope glycoproteinAntiviral vaccinesVirus envelope glycoproteinDengue virusEncephalitis virusFlavivirus genusViral attachmentReceptor bindingWest NileTherapeutic antibodiesMolecular landscapeNile virusVirusSurface epitopesE proteinViruses e.Viral surfaceVirus surface
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 AReceptorsArthropodsBurgdorferiMammalsRepressionSpirochetesTicks
2003
Structurally Distinct Requirements for Binding of P-selectin Glycoprotein Ligand-1 and Sialyl Lewis x to Anaplasma phagocytophilum and P-selectin*
Yago T, Leppänen A, Carlyon JA, Akkoyunlu M, Karmakar S, Fikrig E, Cummings RD, McEver RP. Structurally Distinct Requirements for Binding of P-selectin Glycoprotein Ligand-1 and Sialyl Lewis x to Anaplasma phagocytophilum and P-selectin*. Journal Of Biological Chemistry 2003, 278: 37987-37997. PMID: 12847092, DOI: 10.1074/jbc.m305778200.Peer-Reviewed Original Research
2002
A novel family of anticoagulants from the saliva of Ixodes scapularis
Narasimhan S, Koski RA, Beaulieu B, Anderson JF, Ramamoorthi N, Kantor F, Cappello M, Fikrig E. A novel family of anticoagulants from the saliva of Ixodes scapularis. Insect Molecular Biology 2002, 11: 641-650. PMID: 12421422, DOI: 10.1046/j.1365-2583.2002.00375.x.Peer-Reviewed Original ResearchConceptsN-terminal amino acid sequenceSalivary gland cDNA libraryAmino acid sequenceN-terminal sequenceCDNA libraryAcid sequenceAnticoagulant proteinsIxodes scapularisMolecular approachesTerminal sequenceIntrinsic pathwayEscherichia coliSpecific inhibitorNovel familyProteinSalp14Different functionsTick salivaSequenceBiological activityDose-dependent mannerProtease inhibitorsReversed-phase HPLCParaloguesScapularisDifferential Expression of the p44 Gene Family in the Agent of Human Granulocytic Ehrlichiosis
IJdo JW, Wu C, Telford SR, Fikrig E. Differential Expression of the p44 Gene Family in the Agent of Human Granulocytic Ehrlichiosis. Infection And Immunity 2002, 70: 5295-5298. PMID: 12183586, PMCID: PMC128253, DOI: 10.1128/iai.70.9.5295-5298.2002.Peer-Reviewed Original ResearchConceptsP44 geneDifferential expressionHuman granulocytic ehrlichiosisGene familyAntigenic variationHGE bacteriaTransmission feedingGranulocytic ehrlichiosisGenesHypervariable regionInfected C3H miceP44 expressionTick transmissionExpressionSCID miceC3H miceHGE infectionMurine modelInfected ticksSalivary glandsNymphal ticksMiceTicksEhrlichiosisBacteriaSalp15, an Ixodes scapularis Salivary Protein, Inhibits CD4+ T Cell Activation
Anguita J, Ramamoorthi N, Hovius JW, Das S, Thomas V, Persinski R, Conze D, Askenase PW, Rincón M, Kantor FS, Fikrig E. Salp15, an Ixodes scapularis Salivary Protein, Inhibits CD4+ T Cell Activation. Immunity 2002, 16: 849-859. PMID: 12121666, DOI: 10.1016/s1074-7613(02)00325-4.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsBase SequenceCalcium SignalingCD4-Positive T-LymphocytesCell DivisionDrosophilaFemaleInterleukin-2IxodesLymphocyte ActivationMiceMice, Inbred BALB CMolecular Sequence DataRabbitsRatsReceptors, Antigen, T-CellReceptors, Interleukin-2Salivary Proteins and PeptidesConceptsT cell activationVector-host interactionsI. scapularis salivaCell activationMolecular basisFunctional importanceTCR ligationSalp15ProteinSalivary proteinsTick salivaCalcium fluxIxodes scapularis salivaActivationArthropodsRepressionImmune responseLow productionPleiotropic propertiesHostInhibits CD4T cell-mediated immune responsesVivo
2001
Salp25D, an Ixodes scapularis Antioxidant, Is 1 of 14 Immunodominant Antigens in Engorged Tick Salivary Glands
Das S, Banerjee G, DePonte K, Marcantonio N, Kantor F, Fikrig E. Salp25D, an Ixodes scapularis Antioxidant, Is 1 of 14 Immunodominant Antigens in Engorged Tick Salivary Glands. The Journal Of Infectious Diseases 2001, 184: 1056-1064. PMID: 11574922, DOI: 10.1086/323351.Peer-Reviewed Original ResearchAmino Acid SequenceAnimalsAntigensAntioxidantsCattleCloning, MolecularConsensus SequenceEnzyme-Linked Immunosorbent AssayFemaleGene LibraryGlutathione PeroxidaseGuinea PigsHumansImmunoglobulin GInsect ProteinsIxodesMiceMice, Inbred C3HMolecular Sequence DataNematodaRabbitsRNA, MessengerSalivary GlandsSequence Homology, Amino AcidSpecies SpecificityTime Factors
2000
Attachment of Borrelia burgdorferi within Ixodes scapularis mediated by outer surface protein A
Pal U, de Silva A, Montgomery R, Fish D, Anguita J, Anderson J, Lobet Y, Fikrig E. Attachment of Borrelia burgdorferi within Ixodes scapularis mediated by outer surface protein A. Journal Of Clinical Investigation 2000, 106: 561-569. PMID: 10953031, PMCID: PMC380253, DOI: 10.1172/jci9427.Peer-Reviewed Original Research