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
Repeated 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 host
2021
Grappling 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
2018
Visualization of Microbiota in Tick Guts by Whole-mount In Situ Hybridization.
Moss CE, Robson A, Fikrig E, Narasimhan S. Visualization of Microbiota in Tick Guts by Whole-mount In Situ Hybridization. Journal Of Visualized Experiments 2018 PMID: 29912204, PMCID: PMC6101453, DOI: 10.3791/57758.Peer-Reviewed Original ResearchConceptsTick gutComplex microbial communitiesSitu hybridizationSequencing-based methodsTick genesVector microbiotaMicrobial communitiesParticular bacterial speciesRNA transcriptsResident microorganismsTarget RNAInterspecies interactionsBacterial speciesArthropod vectorsResident bacteriaHuman pathogensMicrobiota interactionsPathogen transmissionTick transmissionIxodes scapularis ticksVector-borne diseasesTick feedingPathogensIntact tissueMicrobiota
2017
Pathogen-mediated manipulation of arthropod microbiota to promote infection
Abraham NM, Liu L, Jutras BL, Yadav AK, Narasimhan S, Gopalakrishnan V, Ansari JM, Jefferson KK, Cava F, Jacobs-Wagner C, Fikrig E. Pathogen-mediated manipulation of arthropod microbiota to promote infection. Proceedings Of The National Academy Of Sciences Of The United States Of America 2017, 114: e781-e790. PMID: 28096373, PMCID: PMC5293115, DOI: 10.1073/pnas.1613422114.Peer-Reviewed Original ResearchConceptsTerminal D-alanine residueHuman pathogensPathogen-mediated manipulationNumerous human pathogensCapacity of bacteriaWay microbesArthropod microbiotaD-alanine residuesA. phagocytophilumAntibacterial proteinsPeritrophic matrixBacterial biofilm formationGut microbiotaMolecular mechanismsBacterial peptidoglycanPentapeptide chainBiofilm formationIAFGPIxodes scapularis ticksDiverse infectious agentsHuman granulocytic anaplasmosisMicrobiotaProteinAntifreeze glycoproteinsAnaplasma phagocytophilum
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
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
2009
The IFITM Proteins Mediate Cellular Resistance to Influenza A H1N1 Virus, West Nile Virus, and Dengue Virus
Brass AL, Huang IC, Benita Y, John SP, Krishnan MN, Feeley EM, Ryan BJ, Weyer JL, van der Weyden L, Fikrig E, Adams DJ, Xavier RJ, Farzan M, Elledge SJ. The IFITM Proteins Mediate Cellular Resistance to Influenza A H1N1 Virus, West Nile Virus, and Dengue Virus. Cell 2009, 139: 1243-1254. PMID: 20064371, PMCID: PMC2824905, DOI: 10.1016/j.cell.2009.12.017.Peer-Reviewed Original ResearchConceptsAntiviral restriction factorsWest Nile virusDengue virusInfluenza A H1N1 virusesNile virusRestriction factorsInterferon type ICellular innate immunityH1N1 virusRespiratory illnessMajor human pathogenViral infectionInnate immunityViral replicationIFITM proteinsInfluenza virusInfluenzaHost cell machineryVirusIFITMsInfectionEndosomal acidificationCellular resistanceType IHuman pathogensEffective siRNA targeting of the 3′ untranslated region of the West Nile virus genome
Anthony KG, Bai F, Krishnan MN, Fikrig E, Koski RA. Effective siRNA targeting of the 3′ untranslated region of the West Nile virus genome. Antiviral Research 2009, 82: 166-168. PMID: 19135091, DOI: 10.1016/j.antiviral.2008.12.007.Peer-Reviewed Original ResearchConceptsWest Nile virusSiRNA targetsSpecific antiviral therapyRelated dengue virusAntiviral therapyWNV pathogenesisShort hairpin RNA sequencesDengue virusWNV replicationTherapeutic potentialViral replicationRNA interferenceAntiviral therapeuticsSiRNA targetingPotential antiviral therapeuticsVero cellsNile virusSequence-specific inhibitorsHuman pathogensUntranslated regionVirusVirus genomeWest Nile virus genomeTargetPathogenesis
2007
Immunity against Ixodes scapularis Salivary Proteins Expressed within 24 Hours of Attachment Thwarts Tick Feeding and Impairs Borrelia Transmission
Narasimhan S, DePonte K, Marcantonio N, Liang X, Royce TE, Nelson KF, Booth CJ, Koski B, Anderson JF, Kantor F, Fikrig E. Immunity against Ixodes scapularis Salivary Proteins Expressed within 24 Hours of Attachment Thwarts Tick Feeding and Impairs Borrelia Transmission. PLOS ONE 2007, 2: e451. PMID: 17505544, PMCID: PMC1866177, DOI: 10.1371/journal.pone.0000451.Peer-Reviewed Original Research