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
2016
Variable Major Proteins as Targets for Specific Antibodies against Borrelia miyamotoi
Wagemakers A, Koetsveld J, Narasimhan S, Wickel M, Deponte K, Bleijlevens B, Jahfari S, Sprong H, Karan LS, Sarksyan DS, van der Poll T, Bockenstedt LK, Bins AD, Platonov AE, Fikrig E, Hovius JW. Variable Major Proteins as Targets for Specific Antibodies against Borrelia miyamotoi. The Journal Of Immunology 2016, 196: 4185-4195. PMID: 27076681, PMCID: PMC5008243, DOI: 10.4049/jimmunol.1600014.Peer-Reviewed Original ResearchConceptsVariable major proteinsB. miyamotoiSerologic testsC3H/HeN miceBorrelia miyamotoiHumoral immune responseInfected SCID miceTick-borne relapsing feverIgM reactivityHumoral immunityHeN miceIgM productionPassive transferSCID miceSerologic assaysCurrent serologic assaysImmune responseImmune serumRelapsing feverSpecific antibodiesProtein 1MiyamotoiIxodes ticksPatientsFever spirochetes
2013
The lipoprotein La7 contributes to Borrelia burgdorferi persistence in ticks and their transmission to naïve hosts
Yang X, Hegde S, Shroder DY, Smith AA, Promnares K, Neelakanta G, Anderson JF, Fikrig E, Pal U. The lipoprotein La7 contributes to Borrelia burgdorferi persistence in ticks and their transmission to naïve hosts. Microbes And Infection 2013, 15: 729-737. PMID: 23774694, PMCID: PMC3769513, DOI: 10.1016/j.micinf.2013.06.001.Peer-Reviewed Original ResearchConceptsComplex enzootic cycleInner membrane proteinB. burgdorferi persistenceProtein-protein interactionsOuter membrane lipoproteinNaïve hostsSpirochete life cycleCo-immunoprecipitation studiesMammalian infectivityMembrane proteinsRedundant rolesMolecular detailsMammalian hostsMembrane lipoproteinGene expressionWild typeInfection cycleLiquid chromatography-mass spectrometry analysisPathogen survivalBiological significanceHost transmissionEnzootic cyclePathogen transmissionSpectrometry analysisLA7
2012
Activation of the RpoN-RpoS regulatory pathway during the enzootic life cycle of Borrelia burgdorferi
Ouyang Z, Narasimhan S, Neelakanta G, Kumar M, Pal U, Fikrig E, Norgard MV. Activation of the RpoN-RpoS regulatory pathway during the enzootic life cycle of Borrelia burgdorferi. BMC Microbiology 2012, 12: 44. PMID: 22443136, PMCID: PMC3320556, DOI: 10.1186/1471-2180-12-44.Peer-Reviewed Original ResearchConceptsRpoN-RpoS regulatory pathwayRpoN-RpoS pathwayExpression of rpoSEnzootic life cycleMammalian infectionRegulatory pathwaysTranscription of rpoSOuter membrane lipoproteinLife cycleB. burgdorferiKey environmental stimuliLyme disease pathogenesisDiverse nichesMembrane lipoproteinMammalian hostsTarget genesTranscription levelsMicrobial survivalLipoprotein geneRpoSOrganism adaptationInfectious cycleFed larvaeIntermolt larvaeSustained transcription
2011
Molecular 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
2008
Borrelia burgdorferi lipoprotein BmpA activates pro-inflammatory responses in human synovial cells through a protein moiety
Yang X, Izadi H, Coleman AS, Wang P, Ma Y, Fikrig E, Anguita J, Pal U. Borrelia burgdorferi lipoprotein BmpA activates pro-inflammatory responses in human synovial cells through a protein moiety. Microbes And Infection 2008, 10: 1300-1308. PMID: 18725314, PMCID: PMC2648844, DOI: 10.1016/j.micinf.2008.07.029.Peer-Reviewed Original ResearchConceptsB mutantsWild-type B. burgdorferiP38 MAP kinase pathwayMAP kinase pathwayHuman synovial cellsSynovial cellsProtein moietyP38 MAP kinaseNF-kappaBLyme arthritisB operonKinase pathwayMAP kinaseRecombinant BmpAPro-inflammatory cytokines TNF-alphaCultured human synovial cellsLipopolysaccharide inhibitorMutantsCytokines TNF-alphaHost inflammatory responsePro-inflammatory responseCytokine responsesIL-1betaTNF-alphaInflammatory responseA Differential Role for BB0365 in the Persistence of Borrelia burgdorferi in Mice and Ticks
Pal U, Dai J, Li X, Neelakanta G, Luo P, Kumar M, Wang P, Yang X, Anderson JF, Fikrig E. A Differential Role for BB0365 in the Persistence of Borrelia burgdorferi in Mice and Ticks. The Journal Of Infectious Diseases 2008, 197: 148-155. PMID: 18171298, DOI: 10.1086/523764.Peer-Reviewed Original ResearchConceptsVertebrate hostsWild-type B. burgdorferiArthropod vectorsB. burgdorferi persistenceB. burgdorferi transcriptomeDiverse murine tissuesSpirochete life cycleLife cycleB. burgdorferi B31Lyme disease agentGene productsMurine tissuesGenesWild rodentsDisease agentsDifferential rolesFeeding ticksB. burgdorferiInfectious isolatesHostBorrelia burgdorferiTicksTranscriptomePersistence of BorreliaMutants
2007
Outer Surface Protein B Is Critical for Borrelia burgdorferi Adherence and Survival within Ixodes Ticks
Neelakanta G, Li X, Pal U, Liu X, Beck DS, DePonte K, Fish D, Kantor FS, Fikrig E. Outer Surface Protein B Is Critical for Borrelia burgdorferi Adherence and Survival within Ixodes Ticks. PLOS Pathogens 2007, 3: e33. PMID: 17352535, PMCID: PMC1817655, DOI: 10.1371/journal.ppat.0030033.Peer-Reviewed Original Research
2004
TROSPA, an Ixodes scapularis Receptor for Borrelia burgdorferi
Pal U, Li X, Wang T, Montgomery RR, Ramamoorthi N, deSilva AM, Bao F, Yang X, Pypaert M, Pradhan D, Kantor FS, Telford S, Anderson JF, Fikrig E. TROSPA, an Ixodes scapularis Receptor for Borrelia burgdorferi. Cell 2004, 119: 457-468. PMID: 15537536, DOI: 10.1016/j.cell.2004.10.027.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsAntibodies, BacterialAntigens, SurfaceBacterial Outer Membrane ProteinsBacterial VaccinesBase SequenceBorrelia burgdorferiCloning, MolecularGene Expression RegulationHost-Parasite InteractionsIntestinesIxodesLipoproteinsMiceMice, Inbred C3HMolecular Sequence DataReceptors, Cell SurfaceRecombinant ProteinsConceptsLyme disease agent Borrelia burgdorferiSurvival of spirochetesTick receptorMammalian hostsRNA interferenceEfficient colonizationTROSPAOuter surface protein ABorrelia burgdorferiPathogen adherencePathogen transmissionProtein AB. burgdorferi outer surface protein AMRNA levelsIxodes scapularisB. burgdorferiColonizationSurface protein AReceptorsArthropodsBurgdorferiMammalsRepressionSpirochetesTicksBorrelia burgdorferi outer surface protein (osp) B expression independent of ospA
Liang FT, Caimano MJ, Radolf JD, Fikrig E. Borrelia burgdorferi outer surface protein (osp) B expression independent of ospA. Microbial Pathogenesis 2004, 37: 35-40. PMID: 15194158, DOI: 10.1016/j.micpath.2004.02.007.Peer-Reviewed Original ResearchAnimalsAntibodies, BacterialAntigens, BacterialAntigens, SurfaceBacterial Outer Membrane ProteinsBacterial VaccinesBorrelia burgdorferiDisease Models, AnimalGene Expression Regulation, BacterialLipoproteinsLyme DiseaseMiceMice, Inbred BALB CMice, SCIDPromoter Regions, GeneticRNA, BacterialRNA, MessengerTicksTranscription, GeneticUSE OF RECOMBINANT ANTIGENS OF BORRELIA BURGDORFERI AND ANAPLASMA PHAGOCYTOPHILUM IN ENZYME-LINKED IMMUNOSORBENT ASSAYS TO DETECT ANTIBODIES IN WHITE-TAILED DEER
Magnarelli LA, IJdo JW, Ramakrishnan U, Henderson DW, Stafford KC, Fikrig E. USE OF RECOMBINANT ANTIGENS OF BORRELIA BURGDORFERI AND ANAPLASMA PHAGOCYTOPHILUM IN ENZYME-LINKED IMMUNOSORBENT ASSAYS TO DETECT ANTIBODIES IN WHITE-TAILED DEER. Journal Of Wildlife Diseases 2004, 40: 249-258. PMID: 15362824, DOI: 10.7589/0090-3558-40.2.249.Peer-Reviewed Original ResearchEssential Role for OspA/B in the Life Cycle of the Lyme Disease Spirochete
Yang XF, Pal U, Alani SM, Fikrig E, Norgard MV. Essential Role for OspA/B in the Life Cycle of the Lyme Disease Spirochete. Journal Of Experimental Medicine 2004, 199: 641-648. PMID: 14981112, PMCID: PMC2213294, DOI: 10.1084/jem.20031960.Peer-Reviewed Original ResearchOspC facilitates Borrelia burgdorferi invasion of Ixodes scapularis salivary glands
Pal U, Yang X, Chen M, Bockenstedt LK, Anderson JF, Flavell RA, Norgard MV, Fikrig E. OspC facilitates Borrelia burgdorferi invasion of Ixodes scapularis salivary glands. Journal Of Clinical Investigation 2004, 113: 220-230. PMID: 14722614, PMCID: PMC311436, DOI: 10.1172/jci19894.Peer-Reviewed Original ResearchMeSH KeywordsActinsAnimalsAntigens, BacterialBacterial Outer Membrane ProteinsBorrelia burgdorferiDisease Models, AnimalEnzyme-Linked Immunosorbent AssayGenetic VectorsImmunoglobulin Fab FragmentsIxodesLipoproteinsLyme DiseaseMiceMice, SCIDMicroscopy, ConfocalModels, GeneticPlasmidsRecombinant ProteinsReverse Transcriptase Polymerase Chain ReactionSalivary GlandsSpirochaetalesTime FactorsUp-RegulationConceptsTick salivary glandsWild-type B. burgdorferiArthropod vectorsWild-type spirochetesTransmission of spirochetesB. burgdorferiMajor surface lipoproteinMammalian hostsGene expressionSalivary glandsOspC geneSurface lipoproteinsSalivary gland colonizationInfectious cloneOuter surface protein CGland colonizationSurface protein CTick gutMutantsOspCUnfed ticksInvasionCritical stepBorrelia burgdorferiSpirochetes
2003
An open-label, nonrandomized, single-center, prospective extension, clinical trial of booster dose schedules to assess the safety profile and immunogenicity of recombinant outer-surface protein A (OspA) Lyme disease vaccine
Schoen RT, Deshefy-Longhi T, Van-Hoecke C, Buscarino C, Fikrig E. An open-label, nonrandomized, single-center, prospective extension, clinical trial of booster dose schedules to assess the safety profile and immunogenicity of recombinant outer-surface protein A (OspA) Lyme disease vaccine. Clinical Therapeutics 2003, 25: 210-224. PMID: 12637121, DOI: 10.1016/s0149-2918(03)90027-0.Peer-Reviewed Original ResearchConceptsLyme disease vaccineFirst booster doseSecond booster doseBooster doseAdverse eventsBooster dosesPrimary seriesMonth 24Disease vaccineClinical trialsEfficacy trialsImmune responseIncidence of AEsPattern of AEsLyme diseaseMost adverse eventsGeometric mean titersTotal IgG antibodiesProportion of subjectsPositive test resultsSeroprotective levelsBooster vaccinationMonth 36Third vaccinationDiary cards
2002
The Lyme Disease Vaccine Takes Its Toll
Thomas V, Fikrig E. The Lyme Disease Vaccine Takes Its Toll. Vector-Borne And Zoonotic Diseases 2002, 2: 217-222. PMID: 12804162, DOI: 10.1089/153036602321653798.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibodies, BacterialAntigens, SurfaceBacterial Outer Membrane ProteinsBacterial VaccinesBorrelia burgdorferiHumansLipoproteinsLyme DiseaseLyme Disease VaccinesMembrane GlycoproteinsMiceMice, KnockoutReceptors, Cell SurfaceToll-Like Receptor 1Toll-Like Receptor 2Toll-Like ReceptorsConceptsTLR2-deficient miceToll-like receptorsPathogen-associated molecular patternsOspA antibodiesSpecific Toll-like receptorsBorrelia burgdorferi outer surface proteinDetectable humoral responseMolecular patternsProtective immune responseLyme disease vaccineDistinct pathogen-associated molecular patternsVaccine recipientsHumoral responseOspA vaccineCell surface expressionOspA vaccinationImmune responseDisease vaccineInnate responseTLR2Protective responseOuter surface proteinsTLR1Lyme diseaseDevelopment of responsesComparative reactivity of human sera to recombinant VlsE and other Borrelia burgdorferi antigens in class-specific enzyme-linked immunosorbent assays for Lyme borreliosis
Magnarelli LA, Lawrenz M, Norris SJ, Fikrig E. Comparative reactivity of human sera to recombinant VlsE and other Borrelia burgdorferi antigens in class-specific enzyme-linked immunosorbent assays for Lyme borreliosis. Journal Of Medical Microbiology 2002, 51: 649-655. PMID: 12171295, DOI: 10.1099/0022-1317-51-8-649.Peer-Reviewed Original ResearchConceptsEnzyme-linked immunosorbent assayIgG antibodiesErythema migransIgM antibodiesLyme borreliosisPhysician-diagnosed erythema migransOnset of illnessVlsE antigenB. burgdorferi infectionBorrelia burgdorferi antigensEnzyme-linked immunosorbentHuman granulocytic ehrlichiosisHuman serumOuter surface protein CRheumatoid arthritisBorrelia burgdorferi sensu strictoOral infectionBurgdorferi infectionFalse-positive reactionsBurgdorferi sensu strictoSera crossLouse-borneLaboratory diagnosisNormal serumGranulocytic ehrlichiosisMolecular Adaptation of Borrelia burgdorferi in the Murine Host
Liang FT, Nelson FK, Fikrig E. Molecular Adaptation of Borrelia burgdorferi in the Murine Host. Journal Of Experimental Medicine 2002, 196: 275-280. PMID: 12119353, PMCID: PMC2193918, DOI: 10.1084/jem.20020770.Peer-Reviewed Original ResearchConceptsLipoprotein geneMolecular adaptationsHost immune selection pressureAnalysis of expressionNovel adaptation mechanismSteps of adaptationSelection pressureLyme disease spirocheteB. burgdorferiMurine hostGenesHost tissuesImmune selection pressureAdaptation mechanismsChronic infectionMurine infectionCritical stepHostBorrelia burgdorferiInfectionAdaptationSpirochetesBurgdorferiInitial inoculumPathogensHyporesponsiveness to vaccination with Borrelia burgdorferi OspA in humans and in TLR1- and TLR2-deficient mice
Alexopoulou L, Thomas V, Schnare M, Lobet Y, Anguita J, Schoen RT, Medzhitov R, Fikrig E, Flavell RA. Hyporesponsiveness to vaccination with Borrelia burgdorferi OspA in humans and in TLR1- and TLR2-deficient mice. Nature Medicine 2002, 8: 878-884. PMID: 12091878, DOI: 10.1038/nm732.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibodies, BacterialAntigens, SurfaceBacterial Outer Membrane ProteinsBacterial VaccinesBorrelia burgdorferiCell SeparationCells, CulturedDrosophila ProteinsHumansInterleukinsLipoproteinsLyme Disease VaccinesMacrophagesMembrane GlycoproteinsMiceMice, KnockoutReceptors, Cell SurfaceSignal TransductionToll-Like Receptor 1Toll-Like Receptor 2Toll-Like ReceptorsConceptsToll-like receptor 1Less tumor necrosis factorTLR2-deficient miceLow antibody titersLyme disease vaccineTumor necrosis factorLow cell surface expressionOuter surface lipoproteinsVaccine recipientsAntibody titersInterleukin-6Cell surface expressionNecrosis factorOspA vaccinationDisease vaccineLow respondersInnate responseTLR2Low titersReceptor 1Substantial titersVaccinationMiceTLR1Borrelia burgdorferiDNA Microarray Assessment of Putative Borrelia burgdorferi Lipoprotein Genes
Liang FT, Nelson FK, Fikrig E. DNA Microarray Assessment of Putative Borrelia burgdorferi Lipoprotein Genes. Infection And Immunity 2002, 70: 3300-3303. PMID: 12011030, PMCID: PMC128019, DOI: 10.1128/iai.70.6.3300-3303.2002.Peer-Reviewed Original Research