2024
Laboratory Management of Mammalian Hosts for Ixodes scapularis -Host-Pathogen Interaction Studies.
Narasimhan S, Cibichakravarthy B, Wu M, Holter M, Walsh C, Goodrich J. Laboratory Management of Mammalian Hosts for Ixodes scapularis -Host-Pathogen Interaction Studies. Comparative Medicine 2024, 74: 235-245. PMID: 39289828, PMCID: PMC11373684, DOI: 10.30802/aalas-cm-24-036.Peer-Reviewed Original ResearchConceptsTick feedingHard-bodied ticksTick speciesArtificial membrane feedingHard ticksMammalian hostsAnimal healthHost-pathogen interaction studiesIxodes scapularisTicksManagement practicesNatural geographic rangePotential vectorsRabbit hostsFeedingHost healthGeographic rangePathogenic organismsInfectious prionsAnimal useRelevant speciesIxodesGuinea pigsLife cycleInteraction studies
2023
A ticking time bomb hidden in plain sight
Narasimhan S, Fish D, Pedra J, Pal U, Fikrig E. A ticking time bomb hidden in plain sight. Science Translational Medicine 2023, 15: eadi7829. PMID: 37851823, DOI: 10.1126/scitranslmed.adi7829.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsSpecific mRNA lipid nanoparticles and acquired resistance to ticks
Matias J, Cui Y, Tang X, Sajid A, Arora G, Wu M, DePonte K, Muramatsu H, Tam Y, Narasimhan S, Pardi N, Weissman D, Fikrig E. Specific mRNA lipid nanoparticles and acquired resistance to ticks. Vaccine 2023, 41: 4996-5002. PMID: 37407406, PMCID: PMC10530371, DOI: 10.1016/j.vaccine.2023.06.081.Peer-Reviewed Original ResearchCroquemort elicits activation of the immune deficiency pathway in ticks
O’Neal A, Singh N, Rolandelli A, Laukaitis H, Wang X, Shaw D, Young B, Narasimhan S, Dutta S, Snyder G, Samaddar S, Marnin L, Butler L, Mendes M, Paz F, Valencia L, Sundberg E, Fikrig E, Pal U, Weber D, Pedra J. Croquemort elicits activation of the immune deficiency pathway in ticks. Proceedings Of The National Academy Of Sciences Of The United States Of America 2023, 120: e2208673120. PMID: 37155900, PMCID: PMC10193931, DOI: 10.1073/pnas.2208673120.Peer-Reviewed Original ResearchConceptsImmune deficiency (IMD) pathwayIMD pathwayNon-insect arthropodsPeptidoglycan recognition proteinsJun N-terminal kinaseN-terminal kinaseArthropod immunityMembrane localizationRecognition proteinsLyme disease spirocheteEcdysteroid synthesisMicrobial moietiesDistinct mechanismsProteinArthropodsPathwayHost defenseElicit activationCroquemortPancrustaceaHomologInsectsActivationCrustaceansKinaseDome1–JAK–STAT signaling between parasite and host integrates vector immunity and development
Rana V, Kitsou C, Dutta S, Ronzetti M, Zhang M, Bernard Q, Smith A, Tomás-Cortázar J, Yang X, Wu M, Kepple O, Li W, Dwyer J, Matias J, Baljinnyam B, Oliver J, Rajeevan N, Pedra J, Narasimhan S, Wang Y, Munderloh U, Fikrig E, Simeonov A, Anguita J, Pal U. Dome1–JAK–STAT signaling between parasite and host integrates vector immunity and development. Science 2023, 379: eabl3837. PMID: 36634189, PMCID: PMC10122270, DOI: 10.1126/science.abl3837.Peer-Reviewed Original ResearchConceptsBlood meal acquisitionMetazoan developmentTick receptorArthropod immunityMammalian hostsSignaling pathwaysReceptor motifEvolutionary dependenceVectorial competenceStem cellsCommunication pathwaysPathwayCritical roleVector immunityHostHigh affinityGenomeAntimicrobial componentsHedgehogJAKMotifMetamorphosisImmunityParasitesPhysiology
2022
Identification of novel conserved Ixodes vaccine candidates; a promising role for non-secreted salivary gland proteins
Trentelman J, de Vogel F, Colstrup E, Sima R, Coumou J, Koetsveld J, Klouwens M, Nayak A, Ersoz J, Barriales D, Tomás-Cortázar J, Narasimhan S, Hajdusek O, Anguita J, Hovius J. Identification of novel conserved Ixodes vaccine candidates; a promising role for non-secreted salivary gland proteins. Vaccine 2022, 40: 7593-7603. PMID: 36357287, DOI: 10.1016/j.vaccine.2022.10.032.Peer-Reviewed Original ResearchConceptsTick salivary gland proteinsAnti-tick vaccinesTick immunityVaccine candidatesSalivary gland proteinsLyme borreliosisNymphal I. ricinusExperimental Lyme borreliosisImmune animalsVaccination studiesTick feedingI. ricinusTick attachmentNymphal ticksPathogen transmissionGuinea pigsIxodes scapularisI. scapularisGland proteinsVaccineCausative agentImmunityMain vectorIdentification of novelPromising roleThe environment, the tick, and the pathogen – It is an ensemble
Couret J, Schofield S, Narasimhan S. The environment, the tick, and the pathogen – It is an ensemble. Frontiers In Cellular And Infection Microbiology 2022, 12: 1049646. PMID: 36405964, PMCID: PMC9666722, DOI: 10.3389/fcimb.2022.1049646.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsTick-pathogen interactionsCritical environmental factorsBiotic factorsAbiotic factorsMammalian hostsEnvironmental microbiotaTick biologyEnsemble of interactionsMolecular understandingMolecular studiesGeographic distributionNorthcentral USAPathogen acquisitionTick-borne diseasesBiologyNew insightsEnvironmental factorsPredominant vectorLyme diseaseTicksInfection prevalenceInteractionPublic health problemPathogensHostTick transmission of Borrelia burgdorferi to the murine host is not influenced by environmentally acquired midgut microbiota
Narasimhan S, Rajeevan N, Graham M, Wu MJ, DePonte K, Marion S, Masson O, O’Neal A, Pedra JHF, Sonenshine DE, Fikrig E. Tick transmission of Borrelia burgdorferi to the murine host is not influenced by environmentally acquired midgut microbiota. Microbiome 2022, 10: 173. PMID: 36253842, PMCID: PMC9575305, DOI: 10.1186/s40168-022-01378-w.Peer-Reviewed Original Research
2021
Tick immunity using mRNA, DNA and protein-based Salp14 delivery strategies
Matias J, Kurokawa C, Sajid A, Narasimhan S, Arora G, Diktas H, Lynn GE, DePonte K, Pardi N, Valenzuela JG, Weissman D, Fikrig E. Tick immunity using mRNA, DNA and protein-based Salp14 delivery strategies. Vaccine 2021, 39: 7661-7668. PMID: 34862075, PMCID: PMC8671329, DOI: 10.1016/j.vaccine.2021.11.003.Peer-Reviewed Original ResearchConceptsTick bite siteTick immunityAntigen deliveryBite siteGuinea pigsDevelopment of vaccinesIxodes scapularis ticksProtein immunizationAntibody responseTick biteVaccine platformLipid nanoparticlesMRNA lipid nanoparticlesMRNA-LNPModel antigenTick salivaEarly hallmarkImmunityTick-borne diseasesScapularis ticksTick challengeErythemaSalivary componentsFactor XaDelivery strategiesmRNA vaccination induces tick resistance and prevents transmission of the Lyme disease agent
Sajid A, Matias J, Arora G, Kurokawa C, DePonte K, Tang X, Lynn G, Wu MJ, Pal U, Strank NO, Pardi N, Narasimhan S, Weissman D, Fikrig E. mRNA vaccination induces tick resistance and prevents transmission of the Lyme disease agent. Science Translational Medicine 2021, 13: eabj9827. PMID: 34788080, DOI: 10.1126/scitranslmed.abj9827.Peer-Reviewed Original ResearchConceptsTick-borne infectionsTick-borne infectious diseaseEngorgement weightDisease agentsTicksTick exposureLyme disease agentGuinea pigsTick biteNormal blood mealBlood mealNucleoside-modified mRNALyme diseasePigsLocal rednessMRNA vaccinationMRNA vaccinesBite siteSalivary proteinsPrevents transmissionInfectious diseasesDiseaseVaccineResistanceEffective inductionThe Lyme Disease agent co-opts adiponectin receptor-mediated signaling in its arthropod vector
Tang X, Cao Y, Arora G, Hwang J, Sajid A, Brown CL, Mehta S, Marín-López A, Chuang YM, Wu MJ, Ma H, Pal U, Narasimhan S, Fikrig E. The Lyme Disease agent co-opts adiponectin receptor-mediated signaling in its arthropod vector. ELife 2021, 10: e72568. PMID: 34783654, PMCID: PMC8639152, DOI: 10.7554/elife.72568.Peer-Reviewed Original ResearchConceptsReceptor-mediated signalingAdiponectin receptorsAdiponectinLyme disease agentLyme disease spirochetePhospholipid metabolismPhosphatidylserine synthase ITick gutReceptor-like proteinMammalian homeostasisArthropod vectorsDisease agentsRNAi assaysRNA interferenceAlternative pathwaySynthase IPathwayMetabolic pathwaysTicksInfectionProbing 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 serumCytochrome b Drug Resistance Mutation Decreases Babesia Fitness in the Tick Stages But Not the Mammalian Erythrocytic Cycle
Chiu JE, Renard I, George S, Pal A, Alday PH, Narasimhan S, Riscoe MK, Doggett JS, Mamoun C. Cytochrome b Drug Resistance Mutation Decreases Babesia Fitness in the Tick Stages But Not the Mammalian Erythrocytic Cycle. The Journal Of Infectious Diseases 2021, 225: 135-145. PMID: 34139755, PMCID: PMC8730496, DOI: 10.1093/infdis/jiab321.Peer-Reviewed Original ResearchConceptsMitochondrial cytochrome bParasite life cycleWild-type alleleTick vectorParasite fitnessCytochrome bMutant parasitesMutant allelesErythrocytic cycleArthropod vectorsNymphal stagesBabesia parasitesMutationsLife cycleFitnessTick stagesResistance mutationsMalaria-like illnessB. microtiAllelesDrug resistance mutationsParasitesHuman babesiosisTicksHostGrappling with the tick microbiome
Narasimhan S, Swei A, Abouneameh S, Pal U, Pedra JHF, Fikrig E. Grappling with the tick microbiome. Trends In Parasitology 2021, 37: 722-733. PMID: 33962878, PMCID: PMC8282638, DOI: 10.1016/j.pt.2021.04.004.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsTick microbiomeRelated tick speciesMultiple human pathogensHost preferenceSequencing technologiesTick biologyHuman pathogensMicrobiomeMechanistic insightsTick speciesLife cycleIxodes pacificusIxodes scapularisIxodid ticksCausative agentNorth AmericaBorrelia burgdorferiPredominant vectorBiological variablesHabitatsPacificusBiologySpeciesPathogens
2020
Fractionation of tick saliva reveals proteins associated with the development of acquired resistance to Ixodes scapularis
Černý J, Lynn G, DePonte K, Ledizet M, Narasimhan S, Fikrig E. Fractionation of tick saliva reveals proteins associated with the development of acquired resistance to Ixodes scapularis. Vaccine 2020, 38: 8121-8129. PMID: 33168347, DOI: 10.1016/j.vaccine.2020.10.087.Peer-Reviewed Original ResearchConceptsTick-borne pathogensTick immunityTick salivaTick vaccinesMultiple tick-borne pathogensIxodes scapularisGuinea pig modelTick salivary antigensTick rejectionTick Ixodes scapularisPig modelTick feedingNortheast USASalivary antigensGlobal medical problemDevelopment of vaccinesTicksMain vectorPathogensSaliva fractionsScapularisMedical problemsImmunityVaccineSalivaRepeat tick exposure elicits distinct immune responses in guinea pigs and mice
Kurokawa C, Narasimhan S, Vidyarthi A, Booth CJ, Mehta S, Meister L, Diktas H, Strank N, Lynn GE, DePonte K, Craft J, Fikrig E. Repeat tick exposure elicits distinct immune responses in guinea pigs and mice. Ticks And Tick-borne Diseases 2020, 11: 101529. PMID: 32993942, PMCID: PMC7530331, DOI: 10.1016/j.ttbdis.2020.101529.Peer-Reviewed Original ResearchConceptsGuinea pigsElicit distinct immune responsesDistinct immune responsesGuinea pig modelLocal blood flowImmune animalsInflammatory pathwaysTick rejectionMechanisms of resistanceImmune responseMouse modelVaccine candidatesBite siteBlood flowPig modelCoagulation pathwayComplement activationAcquired ResistanceProtective antigenTick detachmentTick proteinsBlood mealMiceTick infestationRNA sequencing
2014
Gut Microbiota of the Tick Vector Ixodes scapularis Modulate Colonization of the Lyme Disease Spirochete
Narasimhan S, Rajeevan N, Liu L, Zhao YO, Heisig J, Pan J, Eppler-Epstein R, DePonte K, Fish D, Fikrig E. Gut Microbiota of the Tick Vector Ixodes scapularis Modulate Colonization of the Lyme Disease Spirochete. Cell Host & Microbe 2014, 15: 58-71. PMID: 24439898, PMCID: PMC3905459, DOI: 10.1016/j.chom.2013.12.001.Peer-Reviewed Original ResearchConceptsPeritrophic matrixTranscription factor signal transducerPathogen colonizationLyme disease spirochete Borrelia burgdorferiActivator of transcriptionGut microbiotaArthropod gutsSignal transducerLyme disease spirocheteFunctional linkArthropod vectorsMajor vectorKey glycoproteinsHuman pathogensSpirochete Borrelia burgdorferiGut epitheliumIxodes scapularis ticksColonizationGut epithelial barrierMicrobiotaExpressionGut lumenScapularis ticksBorrelia burgdorferiEpithelial barrier
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
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 HPLCParaloguesScapularis