2021
Probing an Ixodes ricinus salivary gland yeast surface display with tick-exposed human sera to identify novel candidates for an anti-tick vaccine
Trentelman JJA, Tomás-Cortázar J, Knorr S, Barriales D, Hajdusek O, Sima R, Ersoz JI, Narasimhan S, Fikrig E, Nijhof AM, Anguita J, Hovius JW. Probing an Ixodes ricinus salivary gland yeast surface display with tick-exposed human sera to identify novel candidates for an anti-tick vaccine. Scientific Reports 2021, 11: 15745. PMID: 34344917, PMCID: PMC8333314, DOI: 10.1038/s41598-021-92538-9.Peer-Reviewed Original ResearchConceptsTick salivary gland proteinsLyme borreliosisVaccination studiesTick biteTick-borne encephalitis virusB. burgdorferi transmissionMultiple tick bitesYeast surface display libraryHuman infectious diseasesImmunization of rabbitsVaccination platformAnti-tick effectsAnti-tick vaccinesEncephalitis virusImmunodominant antigensInfectious diseasesNon-natural hostsTick immunityTick feedingImmunityBorreliosisBiteVaccineAntigenHuman serumAedes 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
2019
Aedes aegypti NeSt1 Protein Enhances Zika Virus Pathogenesis by Activating Neutrophils
Hastings AK, Uraki R, Gaitsch H, Dhaliwal K, Stanley S, Sproch H, Williamson E, MacNeil T, Marin-Lopez A, Hwang J, Wang Y, Grover JR, Fikrig E. Aedes aegypti NeSt1 Protein Enhances Zika Virus Pathogenesis by Activating Neutrophils. Journal Of Virology 2019, 93: 10.1128/jvi.00395-19. PMID: 30971475, PMCID: PMC6580965, DOI: 10.1128/jvi.00395-19.Peer-Reviewed Original ResearchConceptsVirus infectionBite siteMosquito salivaImmune cellsZika virusLocal immune environmentMosquito bite siteZika virus pathogenesisEarly viral replicationZika virus infectionFactor 1Pathogenesis of flavivirusesVirus-infected mosquitoesVirus-induced pathogenesisCXCL2 expressionImmune environmentPassive immunizationZIKV pathogenesisImmune microenvironmentAntibody responseZIKV replicationVirus pathogenesisMosquito bitesPrimary mouse neutrophilsImmune systemBorrelia burgdorferi chemotaxis toward tick protein Salp12 contributes to acquisition
Murfin KE, Kleinbard R, Aydin M, Salazar SA, Fikrig E. Borrelia burgdorferi chemotaxis toward tick protein Salp12 contributes to acquisition. Ticks And Tick-borne Diseases 2019, 10: 1124-1134. PMID: 31204044, PMCID: PMC7792743, DOI: 10.1016/j.ttbdis.2019.06.002.Peer-Reviewed Original ResearchAedes 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
2018
Host-specific expression of Ixodes scapularis salivary genes
Narasimhan S, Booth CJ, DePonte K, Wu MJ, Liang X, Mohanty S, Kantor F, Fikrig E. Host-specific expression of Ixodes scapularis salivary genes. Ticks And Tick-borne Diseases 2018, 10: 386-397. PMID: 30545615, DOI: 10.1016/j.ttbdis.2018.12.001.Peer-Reviewed Original ResearchConceptsVector-host interactionsTick infestationI. scapularisReservoir hostsNon-reservoir hostsHost-specific expressionRodent reservoir hostsInfected ticksPathogen transmissionZoonotic cycleSalivary genesIxodes scapularisTicksNatural hostScapularisInfestationTick biteLyme diseaseBorrelia burgdorferiLarval stagesPathogensHostPeromyscus leucopusStrong immune responseSalivary transcriptomeA mosquito salivary gland protein partially inhibits Plasmodium sporozoite cell traversal and transmission
Schleicher TR, Yang J, Freudzon M, Rembisz A, Craft S, Hamilton M, Graham M, Mlambo G, Tripathi AK, Li Y, Cresswell P, Sinnis P, Dimopoulos G, Fikrig E. A mosquito salivary gland protein partially inhibits Plasmodium sporozoite cell traversal and transmission. Nature Communications 2018, 9: 2908. PMID: 30046053, PMCID: PMC6060088, DOI: 10.1038/s41467-018-05374-3.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsHost-Parasite InteractionsInsect ProteinsMalariaMosquito VectorsPlasmodiumSalivary GlandsSporozoitesConceptsSalivary gland proteinsCell traversal activityMosquito salivary gland proteinsMosquito salivaGland proteinsCell traversalInfected Anopheles mosquitoesThiol reductaseSporozoite movementVector proteinProteinPlasmodium parasitesAnopheles mosquitoesInitial infectionParasitesHost dermisVector salivaMass spectrometrySporozoitesSalivaMalariaLiverReductaseKey stepHost
2016
Aedes aegypti D7 Saliva Protein Inhibits Dengue Virus Infection
Conway MJ, Londono-Renteria B, Troupin A, Watson AM, Klimstra WB, Fikrig E, Colpitts TM. Aedes aegypti D7 Saliva Protein Inhibits Dengue Virus Infection. PLOS Neglected Tropical Diseases 2016, 10: e0004941. PMID: 27632170, PMCID: PMC5025043, DOI: 10.1371/journal.pntd.0004941.Peer-Reviewed Original ResearchMeSH KeywordsAedesAnimalsDengueDengue VirusFemaleHumansInsect ProteinsMiceSalivaSalivary GlandsSalivary Proteins and PeptidesU937 CellsConceptsSalivary gland extractsDengue virus infectionD7 proteinDengue virus type 1Virus type 1DENV envelope proteinAegypti salivaLymph nodesDENV infectionDENV virionsVirus infectionRelevant arbovirusesType 1InfectionHost skinBlood feedingEnvelope proteinNovel roleBinding assaysSalivaAedes aegyptiGland extractsPrimary vectorHPLC fractionsFeeding
2013
Anopheles gambiae Circumsporozoite Protein–Binding Protein Facilitates Plasmodium Infection of Mosquito Salivary Glands
Wang J, Zhang Y, Zhao YO, Li MW, Zhang L, Dragovic S, Abraham NM, Fikrig E. Anopheles gambiae Circumsporozoite Protein–Binding Protein Facilitates Plasmodium Infection of Mosquito Salivary Glands. The Journal Of Infectious Diseases 2013, 208: 1161-1169. PMID: 23801601, PMCID: PMC3762383, DOI: 10.1093/infdis/jit284.Peer-Reviewed Original ResearchConceptsMosquito salivary glandsCircumsporozoite proteinSalivary glandsPlasmodium organismsPlasmodium circumsporozoite proteinMosquito-borne diseasePlasmodium life cycleSubstantial morbidityPlasmodium infectionMosquito bitesFed bloodGut wallPlasmodium sporozoitesSalivary gland proteinsPlasmodium speciesParasite loadGlandBlood mealInfectionGland proteinsVertebrate hostsVivo bioassaySporozoitesInvasionProtein
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 rolePostgenomic Analyses Reveal Development of Infectious Anaplasma phagocytophilum during Transmission from Ticks to Mice
Mastronunzio JE, Kurscheid S, Fikrig E. Postgenomic Analyses Reveal Development of Infectious Anaplasma phagocytophilum during Transmission from Ticks to Mice. Journal Of Bacteriology 2012, 194: 2238-2247. PMID: 22389475, PMCID: PMC3347074, DOI: 10.1128/jb.06791-11.Peer-Reviewed Original ResearchConceptsOpen reading frameA. phagocytophilum genomeObligate intracellular bacteriaBlood-feeding arthropodsCell surface proteinsMammalian cell cultureRickettsiales orderUncharacterized proteinsRibosomal proteinsEssential proteinsTranscriptome sequencingBacterial adaptationA. phagocytophilumDNA replicationTick salivary glandsPostgenomic analysisReading frameMammalian hostsAnaplasma phagocytophilumDevelopmental transitionsDC-specific markerIntracellular bacteriaTransmission feedingSurface proteinsProtein
2011
Ixodes scapularis salivary gland protein P11 facilitates migration of Anaplasma phagocytophilum from the tick gut to salivary glands
Liu L, Narasimhan S, Dai J, Zhang L, Cheng G, Fikrig E. Ixodes scapularis salivary gland protein P11 facilitates migration of Anaplasma phagocytophilum from the tick gut to salivary glands. EMBO Reports 2011, 12: 1196-1203. PMID: 21921936, PMCID: PMC3207102, DOI: 10.1038/embor.2011.177.Peer-Reviewed Original ResearchIdentification and Characterization of Ixodes scapularis Antigens That Elicit Tick Immunity Using Yeast Surface Display
Schuijt TJ, Narasimhan S, Daffre S, DePonte K, Hovius JW, Veer C, van der Poll T, Bakhtiari K, Meijers JC, Boder ET, van Dam AP, Fikrig E. Identification and Characterization of Ixodes scapularis Antigens That Elicit Tick Immunity Using Yeast Surface Display. PLOS ONE 2011, 6: e15926. PMID: 21246036, PMCID: PMC3016337, DOI: 10.1371/journal.pone.0015926.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigensImmunityImmunizationIxodesNymphPeptide LibraryRabbitsSalivary GlandsTicksYeastsConceptsSalivary antigensTick salivary antigensPotential vaccine candidatesAnti-coagulant activityTick biteImmunization studiesVaccine candidatesAnti-complement activityTick antigensRepeated exposureTick immunityAntigenRabbit serumHall markTicks resultsImmunitySerumYeast surface display libraryRabbitsDisplay libraryIxodes scapularisDrosophila expression systemP19Surface display libraryP8
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 invasionPathogenesisAnaplasma 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
2007
Identification 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 strictoA Tick Antioxidant Facilitates the Lyme Disease Agent's Successful Migration from the Mammalian Host to the Arthropod Vector
Narasimhan S, Sukumaran B, Bozdogan U, Thomas V, Liang X, DePonte K, Marcantonio N, Koski RA, Anderson JF, Kantor F, Fikrig E. A Tick Antioxidant Facilitates the Lyme Disease Agent's Successful Migration from the Mammalian Host to the Arthropod Vector. Cell Host & Microbe 2007, 2: 7-18. PMID: 18005713, PMCID: PMC2699493, DOI: 10.1016/j.chom.2007.06.001.Peer-Reviewed Original ResearchConceptsMammalian hostsComplex feeding sitesLyme disease agent Borrelia burgdorferiSuccessful migrationMammalian responseTick Ixodes scapularisTick salivary glandsReactive oxygen speciesFeeding sitesArthropod vectorsTick proteinsBurgdorferi-infected miceOxygen speciesEfficient vectorCritical roleSpirochete acquisitionIxodes scapularisB. burgdorferiPathogensHostBorrelia burgdorferiI. scapularisInflammatory cellsImmune cellsSurvival advantage
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 anaplasmosisSilencingGenesOrganismsAnaplasma
2005
The Lyme disease agent exploits a tick protein to infect the mammalian host
Ramamoorthi N, Narasimhan S, Pal U, Bao F, Yang XF, Fish D, Anguita J, Norgard MV, Kantor FS, Anderson JF, Koski RA, Fikrig E. The Lyme disease agent exploits a tick protein to infect the mammalian host. Nature 2005, 436: 573-577. PMID: 16049492, PMCID: PMC4306560, DOI: 10.1038/nature03812.Peer-Reviewed Original Research
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