2024
Vaccination to Prevent Lyme Disease: A Movement Towards Anti-Tick Approaches
Johnson E, Hart T, Fikrig E. Vaccination to Prevent Lyme Disease: A Movement Towards Anti-Tick Approaches. The Journal Of Infectious Diseases 2024, 230: s82-s86. PMID: 39140718, PMCID: PMC11322886, DOI: 10.1093/infdis/jiae202.Peer-Reviewed Original ResearchConceptsTransmission of tick-borne pathogensTick-borne pathogensIxodes spp ticksInhibited tick feedingTick feedingDisease vaccineTick vectorWildlife reservoirsOuter surface protein ALyme disease vaccineLyme diseaseTicksBorrelia burgdorferiLyme disease casesPreventing Lyme diseasePathogensFood and Drug AdministrationSurface protein AOspA-based vaccinesVaccineFeedingLymeProtein AFoodPrevent transmission
2023
Adiponectin in the mammalian host influences ticks’ acquisition of the Lyme disease pathogen Borrelia
Tang X, Cao Y, Booth C, Arora G, Cui Y, Matias J, Fikrig E. Adiponectin in the mammalian host influences ticks’ acquisition of the Lyme disease pathogen Borrelia. PLOS Biology 2023, 21: e3002331. PMID: 37862360, PMCID: PMC10619873, DOI: 10.1371/journal.pbio.3002331.Peer-Reviewed Original ResearchConceptsAdipocyte-derived hormoneBite siteAdiponectin-deficient miceInfiltration of neutrophilsTick bite sitePro-inflammatory responseWild-type animalsIxodes scapularis ticksIL-1βVascular leakageHistamine releaseTick biteAdiponectinInfectious diseasesLyme disease agentBlood feeding arthropodsBorrelia burgdorferiScapularis ticksAnimal infectious diseasesBlood feedingB. burgdorferi survivalHuman bloodHormonePathogen acquisitionMammalian hosts
2022
Use of host lipids by the Lyme disease spirochete may lead to biomarkers
Arora G, Hart T, Fikrig E. Use of host lipids by the Lyme disease spirochete may lead to biomarkers. Journal Of Clinical Investigation 2022, 132: e158254. PMID: 35289311, PMCID: PMC8920323, DOI: 10.1172/jci158254.Peer-Reviewed Original ResearchConceptsB. burgdorferi infectionLyme diseaseBurgdorferi infectionCareful clinical assessmentCommon tick-borne diseaseAnti-lipid antibodiesProduction of antibodiesTick-borne diseaseHost lipidsAntibody titersLyme disease agent Borrelia burgdorferiClinical assessmentCurrent biomarkersMurine modelDiseaseSerum samplesLyme disease spirocheteAntibodiesBorrelia burgdorferiInfectionBiomarkersPatientsLipidsSyphilisPhosphatidic acid
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
2020
A human secretome library screen reveals a role for Peptidoglycan Recognition Protein 1 in Lyme borreliosis
Gupta A, Arora G, Rosen CE, Kloos Z, Cao Y, Cerny J, Sajid A, Hoornstra D, Golovchenko M, Rudenko N, Munderloh U, Hovius JW, Booth CJ, Jacobs-Wagner C, Palm NW, Ring AM, Fikrig E. A human secretome library screen reveals a role for Peptidoglycan Recognition Protein 1 in Lyme borreliosis. PLOS Pathogens 2020, 16: e1009030. PMID: 33175909, PMCID: PMC7657531, DOI: 10.1371/journal.ppat.1009030.Peer-Reviewed Original ResearchConceptsPeptidoglycan recognition protein 1B. burgdorferi infectionB. burgdorferiBurgdorferi infectionHost responseLow serum IgG levelsCommon vector-borne illnessDiverse host responsesSerum IgG levelsProtein 1Vector-borne illnessImmune dysregulationIgG levelsBorreliacidal activityBurgdorferi sensu latoHuman extracellular proteinsSpirochete burdenTick biteB. burgdorferi sensu latoSpirochete Borrelia burgdorferiNervous systemLyme borreliosisLyme diseaseInfectionBorrelia burgdorferi
2019
Borrelia miyamotoi infection leads to cross-reactive antibodies to the C6 peptide in mice and men
Koetsveld J, Platonov A, Kuleshov K, Wagemakers A, Hoornstra D, Ang W, Szekeres S, van Duijvendijk G, Fikrig E, Embers M, Sprong H, Hovius J. Borrelia miyamotoi infection leads to cross-reactive antibodies to the C6 peptide in mice and men. Clinical Microbiology And Infection 2019, 26: 513.e1-513.e6. PMID: 31404672, DOI: 10.1016/j.cmi.2019.07.026.Peer-Reviewed Original ResearchConceptsCross-reactive antibodiesC6 peptideEnzyme immunoassayLyme borreliosisBorrelia miyamotoi infectionBMD patientsExperimental murine infectionC6 enzyme immunoassayAvailable immunoblotNegative immunoblotMiyamotoi infectionTick bitePatient seraMurine infectionPatientsReactivity testingInfectionVlsE proteinBorrelia miyamotoiBorrelia burgdorferiMice
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 transcriptomeDirect Diagnostic Tests for Lyme Disease
Schutzer SE, Body BA, Boyle J, Branson BM, Dattwyler RJ, Fikrig E, Gerald NJ, Gomes-Solecki M, Kintrup M, Ledizet M, Levin AE, Lewinski M, Liotta LA, Marques A, Mead PS, Mongodin EF, Pillai S, Rao P, Robinson WH, Roth KM, Schriefer ME, Slezak T, Snyder JL, Steere AC, Witkowski J, Wong SJ, Branda JA. Direct Diagnostic Tests for Lyme Disease. Clinical Infectious Diseases 2018, 68: 1052-1057. PMID: 30307486, PMCID: PMC6399434, DOI: 10.1093/cid/ciy614.Peer-Reviewed Original ResearchHuman Borrelia miyamotoi infection in California: Serodiagnosis is complicated by multiple endemic Borrelia species
Krause PJ, Carroll M, Fedorova N, Brancato J, Dumouchel C, Akosa F, Narasimhan S, Fikrig E, Lane RS. Human Borrelia miyamotoi infection in California: Serodiagnosis is complicated by multiple endemic Borrelia species. PLOS ONE 2018, 13: e0191725. PMID: 29420552, PMCID: PMC5805228, DOI: 10.1371/journal.pone.0191725.Peer-Reviewed Original ResearchConceptsBorrelia miyamotoi infectionMiyamotoi infectionB. miyamotoiB. miyamotoi diseaseB. miyamotoi infectionB. burgdorferi infectionHealth care professionalsWhole cell lysatesSeropositive subjectsSufficient serumClinical dataBurgdorferi infectionAntibody assaysSeropositive samplesCare professionalsBorrelia antigensInfectionSerumAntibodiesBorrelia burgdorferiAntigenI. pacificus ticksMiyamotoiTick infectionFever spirochetes
2017
Advances in Serodiagnostic Testing for Lyme Disease Are at Hand
Branda JA, Body BA, Boyle J, Branson BM, Dattwyler RJ, Fikrig E, Gerald NJ, Gomes-Solecki M, Kintrup M, Ledizet M, Levin AE, Lewinski M, Liotta LA, Marques A, Mead PS, Mongodin EF, Pillai S, Rao P, Robinson WH, Roth KM, Schriefer ME, Slezak T, Snyder J, Steere AC, Witkowski J, Wong SJ, Schutzer SE. Advances in Serodiagnostic Testing for Lyme Disease Are at Hand. Clinical Infectious Diseases 2017, 66: 1133-1139. PMID: 29228208, PMCID: PMC6019075, DOI: 10.1093/cid/cix943.Peer-Reviewed Original ResearchConceptsSerodiagnostic testingEnzyme immunoassayLyme diseaseIndirect fluorescence antibodySerologic assaysImmunoglobulin MEarly infectionFluorescence antibodyTesting protocolAlternative testing protocolsBorrelia burgdorferiB. burgdorferiWestern immunoblotAntigenDiseaseAntibodiesBurgdorferiLow sensitivitySynthetic peptidesAssaysArtificial Infection of Ticks with Borrelia burgdorferi Using a Microinjection Method and Their Detection In Vivo Using Quantitative PCR Targeting flaB RNA
Smith AA, Yang X, Fikrig E, Pal U. Artificial Infection of Ticks with Borrelia burgdorferi Using a Microinjection Method and Their Detection In Vivo Using Quantitative PCR Targeting flaB RNA. Methods In Molecular Biology 2017, 1690: 105-114. PMID: 29032540, DOI: 10.1007/978-1-4939-7383-5_9.Peer-Reviewed Original ResearchModulation of the tick gut milieu by a secreted tick protein favors Borrelia burgdorferi colonization
Narasimhan S, Schuijt TJ, Abraham NM, Rajeevan N, Coumou J, Graham M, Robson A, Wu MJ, Daffre S, Hovius JW, Fikrig E. Modulation of the tick gut milieu by a secreted tick protein favors Borrelia burgdorferi colonization. Nature Communications 2017, 8: 184. PMID: 28775250, PMCID: PMC5543126, DOI: 10.1038/s41467-017-00208-0.Peer-Reviewed Original ResearchConceptsB. burgdorferi colonizationTick gutImmune responseRNA interference-mediated silencingGut microbiomeLyme disease agentBorrelia burgdorferiB. burgdorferiGutTick proteinsVivo resultsBurgdorferiPixRAbrogationTick Ixodes scapularisArthropod vectorsDisease agentsGut proteinsIxodes scapularisAlterationsGut genesMicrobiomeTick biologyMiceBacterial biofilm formationInfection-derived lipids elicit an immune deficiency circuit in arthropods
Shaw DK, Wang X, Brown LJ, Chávez AS, Reif KE, Smith AA, Scott AJ, McClure EE, Boradia VM, Hammond HL, Sundberg EJ, Snyder GA, Liu L, DePonte K, Villar M, Ueti MW, de la Fuente J, Ernst RK, Pal U, Fikrig E, Pedra JH. Infection-derived lipids elicit an immune deficiency circuit in arthropods. Nature Communications 2017, 8: 14401. PMID: 28195158, PMCID: PMC5316886, DOI: 10.1038/ncomms14401.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAnaplasma marginaleAnaplasma phagocytophilumAnimalsArthropodsBorrelia burgdorferiCarrier ProteinsDisease Models, AnimalDrosophila melanogasterDrosophila ProteinsEscherichia coliFas-Associated Death Domain ProteinGene SilencingHEK293 CellsHumansImmunologic Deficiency SyndromesIxodesLipidsLyme DiseasePhosphatidylglycerolsRecombinant ProteinsRNA, Small InterferingSignal TransductionTranscription FactorsUbiquitin-Conjugating EnzymesUbiquitin-Protein LigasesX-Linked Inhibitor of Apoptosis ProteinConceptsAdaptor molecule FasImmune deficiency (IMD) pathwayPeptidoglycan recognition proteinsE3 ubiquitin ligaseLyme disease spirochete Borrelia burgdorferiIMD pathwayGram-negative bacteriaRecognition proteinsUbiquitin ligaseDeath domainApoptosis proteinDistinct bacteriaBiochemical interactionsMolecule FasSpirochete Borrelia burgdorferiReceptor networkA. marginaleProteinAnaplasma phagocytophilumBacteriaPathwayBorrelia burgdorferiInsectsLipidsArthropods
2015
Ixodes scapularis dystroglycan-like protein promotes Borrelia burgdorferi migration from the gut
Coumou J, Narasimhan S, Trentelman JJ, Wagemakers A, Koetsveld J, Ersoz JI, Oei A, Fikrig E, Hovius JW. Ixodes scapularis dystroglycan-like protein promotes Borrelia burgdorferi migration from the gut. Journal Of Molecular Medicine 2015, 94: 361-370. PMID: 26594018, PMCID: PMC4803822, DOI: 10.1007/s00109-015-1365-0.Peer-Reviewed Original ResearchConceptsB. burgdorferi transmissionTick gutLyme borreliosisTick feedingMurine modelVaccine targetsUninfected ticksRNA interferenceInfected ticksSalivary glandsBorrelia burgdorferiPotential targetGut tissueB. burgdorferiCausative agentIxodes ticksGutPrevious screeningTick proteinsGut cellsBurgdorferiMiceTicks resultsBorreliosisConfocal microscopy
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 pathogensSERUM ANTIBODIES TO BORRELIA BURGDORFERI, ANAPLASMA PHAGOCYTOPHILUM, AND BABESIA MICROTI IN RECAPTURED WHITE-FOOTED MICE
Magnarelli LA, Williams SC, Norris SJ, Fikrig E. SERUM ANTIBODIES TO BORRELIA BURGDORFERI, ANAPLASMA PHAGOCYTOPHILUM, AND BABESIA MICROTI IN RECAPTURED WHITE-FOOTED MICE. Journal Of Wildlife Diseases 2013, 49: 294-302. PMID: 23568904, PMCID: PMC3712766, DOI: 10.7589/2012-06-172.Peer-Reviewed Original ResearchConceptsB. microtiA. phagocytophilumB. burgdorferiBabesia microtiSolid-phase enzyme-linked immunosorbent assayAnaplasma phagocytophilumMouse immune systemEnzyme-linked immunosorbent assayIndirect fluorescent antibodyAntibody statusAntibody titersBorrelia burgdorferi sensu strictoSerum antibodiesTotal antibodyAntibody prevalenceNegative statusBurgdorferi sensu strictoImmune systemPatent infectionsEnd pointMiceImmunosorbent assayAntibodiesBorrelia burgdorferiFluorescent antibody
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 ticksMolecular Interactions that Enable Movement of the Lyme Disease Agent from the Tick Gut into the Hemolymph
Zhang L, Zhang Y, Adusumilli S, Liu L, Narasimhan S, Dai J, Zhao YO, Fikrig E. Molecular Interactions that Enable Movement of the Lyme Disease Agent from the Tick Gut into the Hemolymph. PLOS Pathogens 2011, 7: e1002079. PMID: 21695244, PMCID: PMC3111543, DOI: 10.1371/journal.ppat.1002079.Peer-Reviewed Original ResearchConceptsLyme disease agentB. burgdorferi burdenTick gutOuter surface lipoproteinsTick gut proteinsSalivary gland infectionIxodes scapularis ticksInfection resultsMouse infectionDisease agentsGland infectionLyme diseaseBorrelia burgdorferiScapularis ticksB. burgdorferiCausative agentInfectionBurgdorferiGutGut proteinsSpirochetesTick hemolymphTicksAgentsHemolymph
2009
Antibodies against a Tick Protein, Salp15, Protect Mice from the Lyme Disease Agent
Dai J, Wang P, Adusumilli S, Booth CJ, Narasimhan S, Anguita J, Fikrig E. Antibodies against a Tick Protein, Salp15, Protect Mice from the Lyme Disease Agent. Cell Host & Microbe 2009, 6: 482-492. PMID: 19917502, PMCID: PMC2843562, DOI: 10.1016/j.chom.2009.10.006.Peer-Reviewed Original ResearchConceptsArthropod-borne pathogensTick-borne BorreliaTick salivary proteinsTick proteinsB. burgdorferiLyme diseaseDisease agentsTick-borne illnessB. burgdorferi infectionLyme disease agentHuman vaccinesSalp15Infection of miceB. burgdorferi antigensMicrobial toxinsMammalian hostsBorrelia burgdorferiPathogensMechanism of actionBurgdorferi infectionProtect miceMedical importanceBurgdorferiProtective capacityMice