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 studiesBacterial reprogramming of tick metabolism impacts vector fitness and susceptibility to infection
Samaddar S, Rolandelli A, O’Neal A, Laukaitis-Yousey H, Marnin L, Singh N, Wang X, Butler L, Rangghran P, Kitsou C, Cabrera Paz F, Valencia L, R. Ferraz C, Munderloh U, Khoo B, Cull B, Rosche K, Shaw D, Oliver J, Narasimhan S, Fikrig E, Pal U, Fiskum G, Polster B, Pedra J. Bacterial reprogramming of tick metabolism impacts vector fitness and susceptibility to infection. Nature Microbiology 2024, 9: 2278-2291. PMID: 38997520, DOI: 10.1038/s41564-024-01756-0.Peer-Reviewed Original ResearchMetabolic reprogrammingInfection of tick cellsInvestigate metabolic reprogrammingTick cellsLyme disease spirochete Borrelia burgdorferiSusceptibility to infectionArthropod-borne pathogensMetabolomics approachRickettsia buchneriHuman pathogensMetabolite allocationDiminished survivalBacterium Anaplasma phagocytophilumSpirochete Borrelia burgdorferiAcid metabolismA. phagocytophilum infectionInterspecies relationshipsElevated levelsInfectionFeeding impairmentHuman granulocytic anaplasmosisMetabolic responseArthropod vectorsI. scapularisPathogens
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 StatementsTick salivary glycans – a sugar-coated tick bite
Karim S, Leyva-Castillo J, Narasimhan S. Tick salivary glycans – a sugar-coated tick bite. Trends In Parasitology 2023, 39: 1100-1113. PMID: 37838514, DOI: 10.1016/j.pt.2023.09.012.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsCertain tick speciesDisease-causing pathogensNon-natural host speciesTick resistanceTick speciesTick feedingTick salivaPathogen transmissionTick bite siteMeat consumptionHematophagous arthropodsHost speciesTick biteRed meat consumptionMeat allergySuccessful feedingRed meat allergySpeciesTicksFeedingAllergic responsesImmune responseArthropodsCurrent knowledgePathogensSpecific 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 activationCroquemortPancrustaceaHomologInsectsActivationCrustaceansKinaseRepeated Tick Infestations Impair Borrelia burgdorferi Transmission in a Non-Human Primate Model of Tick Feeding
Narasimhan S, Booth C, Philipp M, Fikrig E, Embers M. Repeated Tick Infestations Impair Borrelia burgdorferi Transmission in a Non-Human Primate Model of Tick Feeding. Pathogens 2023, 12: 132. PMID: 36678479, PMCID: PMC9861725, DOI: 10.3390/pathogens12010132.Peer-Reviewed Original ResearchNon-human primatesImmune responseLyme diseaseTick transmissionAnimal modelsGuinea pigsNon-human primate modelProtective immune responseTick feedingTick infestationRobust immune responseTick salivary antigensElicit immune responsesHuman Lyme diseaseClinical manifestationsHuman pathogensPrimate modelSalivary antigensNon-natural hostsVaccine targetsDiseaseVaccine discoveryTick resistanceBorreliaNatural hostDome1–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 ResearchImmunization of guinea pigs with cement extract induces resistance against Ixodes scapularis ticks
Lynn GE, Černý J, Kurokawa C, Diktaş H, Matias J, Sajid A, Arora G, DePonte K, Narasimhan S, Fikrig E. Immunization of guinea pigs with cement extract induces resistance against Ixodes scapularis ticks. Ticks And Tick-borne Diseases 2022, 13: 102017. PMID: 35963188, DOI: 10.1016/j.ttbdis.2022.102017.Peer-Reviewed Original ResearchTick salivaAnti-tick vaccinesTick-host interfaceSpecific protective antigensTick engorgement weightIxodes scapularis ticksTick speciesTick feedingEngorgement weightFeeding ticksHost resistanceTickborne pathogensDisease agentsAnimal hostsIxodes scapularisFemale I. scapularisI. scapularisScapularis ticksTicksImportant vectorTick detachmentPrimary vectorMidgut extractsProtective antigenHematophagous parasitesBorrelia miyamotoi Meningoencephalitis in an Immunocompetent Patient
Gandhi S, Narasimhan S, Workineh A, Mamula M, Yoon J, Krause PJ, Farhadian SF. Borrelia miyamotoi Meningoencephalitis in an Immunocompetent Patient. Open Forum Infectious Diseases 2022, 9: ofac295. PMID: 35873293, PMCID: PMC9301576, DOI: 10.1093/ofid/ofac295.Peer-Reviewed Original ResearchEditorial: Tick Saliva: Secret to Blood Feeding Success
Sonenshine DE, Nuttall PA, Narasimhan S. Editorial: Tick Saliva: Secret to Blood Feeding Success. Frontiers In Cellular And Infection Microbiology 2022, 12: 885240. PMID: 35372110, PMCID: PMC8968142, DOI: 10.3389/fcimb.2022.885240.Commentaries, Editorials and LettersCorrection: The 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. Correction: The Lyme disease agent co-opts adiponectin receptor-mediated signaling in its arthropod vector. ELife 2022, 11: e77794. PMID: 35179491, PMCID: PMC8856650, DOI: 10.7554/elife.77794.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 pathwaysTicksInfectionHygromycin A in the Lymelight
Arnaboldi PM, Narasimhan S. Hygromycin A in the Lymelight. Cell Host & Microbe 2021, 29: 1599-1601. PMID: 34762823, DOI: 10.1016/j.chom.2021.10.007.Commentaries, Editorials and LettersProbing 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 serum