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
Croquemort 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 activationCroquemortPancrustaceaHomologInsectsActivationCrustaceansKinase
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 ResearchUse 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
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. 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 ResearchMeSH KeywordsAnimalsArthropod ProteinsArthropod VectorsBorrelia burgdorferiIxodesLyme DiseasePhospholipidsReceptors, AdiponectinRNA InterferenceTranscriptomeConceptsReceptor-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 serum
2020
Interactions Between Ticks and Lyme Disease Spirochetes.
Pal U, Kitsou C, Drecktrah D, Yaş ÖB, Fikrig E. Interactions Between Ticks and Lyme Disease Spirochetes. Current Issues In Molecular Biology 2020, 42: 113-144. PMID: 33289683, PMCID: PMC8045411, DOI: 10.21775/cimb.042.113.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsArachnid VectorsBorrelia burgdorferiHost-Pathogen InteractionsHumansIxodesLife Cycle StagesLyme DiseaseNorthwestern United StatesTicksConceptsComplex enzootic life cycleEnzootic life cycleMammalian reservoir hostsMolecular interactionsLife cycleDiscrete molecular interactionsVariety of animalsRelated ticksVertebrate hostsLyme disease spirocheteArthropod vectorsSensu latoPathogen persistenceWild rodentsBacterial pathogensReservoir hostsCritical roleTick-transmitted infectionsMain vectorNortheastern United StatesPast discoveriesHostTicksArthropodsSpirochetesAn Ixodes scapularis Protein Disulfide Isomerase Contributes to Borrelia burgdorferi Colonization of the Vector
Cao Y, Rosen C, Arora G, Gupta A, Booth CJ, Murfin KE, Cerny J, Lopez A, Chuang YM, Tang X, Pal U, Ring A, Narasimhan S, Fikrig E. An Ixodes scapularis Protein Disulfide Isomerase Contributes to Borrelia burgdorferi Colonization of the Vector. Infection And Immunity 2020, 88: 10.1128/iai.00426-20. PMID: 32928964, PMCID: PMC7671890, DOI: 10.1128/iai.00426-20.Peer-Reviewed Original ResearchConceptsTick gutTick bite siteVector-host interfaceAbility of spirochetesProtein disulfide isomerase A3Infected vertebrate hostsInflammatory responseBite siteLyme diseaseVertebrate hostsGutTick proteinsAdditional targetsMiceSpirochete life cycleSpirochete survivalArthropod vectorsSpirochetesRNA interferenceIllnessTicksA 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 ResearchMeSH KeywordsAnimalsBorrelia burgdorferiCytokinesGene LibraryHumansLyme DiseaseMiceMice, Inbred BALB CConceptsPeptidoglycan 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
Protective Immunity and New Vaccines for Lyme Disease
Gomes-Solecki M, Arnaboldi PM, Backenson PB, Benach JL, Cooper CL, Dattwyler RJ, Diuk-Wasser M, Fikrig E, Hovius JW, Laegreid W, Lundberg U, Marconi RT, Marques AR, Molloy P, Narasimhan S, Pal U, Pedra JHF, Plotkin S, Rock DL, Rosa P, Telford SR, Tsao J, Yang XF, Schutzer SE. Protective Immunity and New Vaccines for Lyme Disease. Clinical Infectious Diseases 2019, 70: 1768-1773. PMID: 31620776, PMCID: PMC7155782, DOI: 10.1093/cid/ciz872.Peer-Reviewed Original ResearchConceptsLyme diseaseCommon tick-borne illnessTick-borne illnessB. burgdorferi infectionBorrelia burgdorferi sensu latoMechanism of actionDirect vaccinationB. burgdorferi proteinsProtective immunityBurgdorferi sensu latoVaccination strategiesBurgdorferi infectionFirst vaccineImmune pathwaysNew vaccinesNumber of casesTick immunityDiseaseVaccineB. burgdorferiHuman hostTick proteinsInfectionImmunityPathogen transmissionPolymicrobial Nature of Tick-Borne Diseases
Sanchez-Vicente S, Tagliafierro T, Coleman J, Benach J, Tokarz R, Azad A, Fikrig E, Munderloh U, Telford S. Polymicrobial Nature of Tick-Borne Diseases. MBio 2019, 10: e02055-19. PMID: 31506314, PMCID: PMC6737246, DOI: 10.1128/mbio.02055-19.Peer-Reviewed Original ResearchConceptsPolymicrobial infectionsClinical spectrumTick-borne diseasesFatal infectionPowassan virusDisproportionate incidenceTick-borne diseaseDifficult diagnosisNew pathogensNew agentsPolymicrobial natureDisease severityInfectionDiseaseLyme diseasePrevalent pathogenBorreliaHigh rateIncidenceDiagnosisSeverityRickettsiaTick vectorVirusClimate changeBorrelia burgdorferi chemotaxis toward tick protein Salp12 contributes to acquisition
Murfin KE, Kleinbard R, Aydin M, Salazar SA, Fikrig E. Borrelia burgdorferi chemotaxis toward tick protein Salp12 contributes to acquisition. Ticks And Tick-borne Diseases 2019, 10: 1124-1134. PMID: 31204044, PMCID: PMC7792743, DOI: 10.1016/j.ttbdis.2019.06.002.Peer-Reviewed Original ResearchThe role of Mannose Binding Lectin in the immune response against Borrelia burgdorferi sensu lato
Coumou J, Wagemakers A, Narasimhan S, Schuijt TJ, Ersoz JI, Oei A, de Boer OJ, Roelofs JJTH, Fikrig E, Hovius JW. The role of Mannose Binding Lectin in the immune response against Borrelia burgdorferi sensu lato. Scientific Reports 2019, 9: 1431. PMID: 30723261, PMCID: PMC6363739, DOI: 10.1038/s41598-018-37922-8.Peer-Reviewed Original ResearchConceptsMannose-Binding LectinB. burgdorferiImmune responseComplement systemRole of MBLMBL-deficient miceWhole blood stimulationIgG serum antibodiesB. burgdorferi infectionB. burgdorferi numbersHost complement systemMechanism warrants further investigationSerum-sensitive isolatesBorrelia burgdorferi sensu lato groupWarrants further investigationBorrelia burgdorferi sensu latoLater time pointsBinding lectinsSevere courseBlood stimulationDetectable antibodiesBurgdorferi sensu latoSerum antibodiesMBL deficiencyDeficient mice
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 ResearchMeSH KeywordsBorrelia burgdorferiDiagnostic Tests, RoutineGenomicsHigh-Throughput Screening AssaysHumansLyme DiseasePolymerase Chain ReactionSerologic TestsVisualization 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 ResearchMeSH KeywordsAnimalsBorrelia burgdorferiElectrophoresis, Polyacrylamide GelHumansIn Situ HybridizationIxodesMicrobiotaConceptsTick 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
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