2024
Bacterial 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 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 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
Tick 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 parasitesCorrection: 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 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 serumGrappling 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 variablesHabitatsPacificusBiologySpeciesPathogensPotential impacts of climate change on medically important tick species in North America.
Lynn G, Narasimhan S, Fikrig E. Potential impacts of climate change on medically important tick species in North America. 2021, 145-151. DOI: 10.1079/9781789249637.0021.Chapters
2020
Acquired tick resistance: The trail is hot
Narasimhan S, Kurokawa C, DeBlasio M, Matias J, Sajid A, Pal U, Lynn G, Fikrig E. Acquired tick resistance: The trail is hot. Parasite Immunology 2020, 43: e12808. PMID: 33187012, PMCID: PMC8058238, DOI: 10.1111/pim.12808.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsFractionation 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
2018
Visualization of Microbiota in Tick Guts by Whole-mount <em>In Situ</em> Hybridization
Moss C, Robson A, Fikrig E, Narasimhan S. Visualization of Microbiota in Tick Guts by Whole-mount In Situ Hybridization. Journal Of Visualized Experiments 2018 DOI: 10.3791/57758-v.Peer-Reviewed Original Research
2017
Chapter 14 Translation of Saliva Proteins Into Tools to Prevent Vector-Borne Disease Transmission
Narasimhan S, Schleicher T, Fikrig E. Chapter 14 Translation of Saliva Proteins Into Tools to Prevent Vector-Borne Disease Transmission. 2017, 249-300. DOI: 10.1016/b978-0-12-805360-7.00014-9.ChaptersPathogen transmissionArthropod vectorsVector-pathogen interactionsBlood mealVector salivaVector-Borne Disease TransmissionTransmit pathogensMolecular understandingHematophagous arthropodsHost immune responseMicrobesArthropodsImmune responseSalivary proteinsPathogensHostArthropod salivaMicroorganism transmission