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
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
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 transmissionThe 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
Direct 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
2010
Immunization with Adenoviral-expressed salivary gland proteins (SALPs) decreases spirochete load in a murine model of Lyme borreliosis (52.2)
Ullmann A, Dolan M, Fikrig E, Piesman J, Zeidner N. Immunization with Adenoviral-expressed salivary gland proteins (SALPs) decreases spirochete load in a murine model of Lyme borreliosis (52.2). The Journal Of Immunology 2010, 184: 52.2-52.2. DOI: 10.4049/jimmunol.184.supp.52.2.Peer-Reviewed Original ResearchBurgdorferi infectionMurine modelTick salivary proteinsC3H/HeJ miceDendritic cell expressionCellular immune responsesBorrelia burgdorferi infectionB. burgdorferi infectionLeast partial protectionSalivary proteinsSalivary gland proteinsImmunized miceSpecific immunitySpirochete burdenImmunomodulatory factorsHeJ miceVaccination techniqueImmune responseI. scapularis ticksTarget organsProtein antibodiesCell expressionSpirochete loadTick salivaLyme borreliosis
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 capacityMiceLate Manifestations of Lyme Borreliosis
Hovius J, van Dam A, Fikrig E. Late Manifestations of Lyme Borreliosis. 2009, 9-25. DOI: 10.1128/9781555815486.ch2.Peer-Reviewed Original ResearchLyme borreliosisObjective clinical manifestationsFrequent clinical signsB. burgdorferiB. burgdorferi infectionHost immune responseCommon vector-borne diseaseClinical manifestationsErythema migransAntibiotic treatmentClinical signsBurgdorferi infectionImmune responsePositive culturesLate manifestationTick-borne pathogensLyme diseaseBorreliosisBorrelia burgdorferiDiseaseCausative agentB. afzeliiB. gariniiInfected tissuesBurgdorferiThe Urokinase Receptor (uPAR) Facilitates Clearance of Borrelia burgdorferi
Hovius JW, Bijlsma MF, van der Windt GJ, Wiersinga WJ, Boukens BJ, Coumou J, Oei A, de Beer R, de Vos AF, van 't Veer C, van Dam AP, Wang P, Fikrig E, Levi MM, Roelofs JJ, van der Poll T. The Urokinase Receptor (uPAR) Facilitates Clearance of Borrelia burgdorferi. PLOS Pathogens 2009, 5: e1000447. PMID: 19461880, PMCID: PMC2678258, DOI: 10.1371/journal.ppat.1000447.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsArthritis, InfectiousBorrelia burgdorferiCell MovementHeartHistocytochemistryHumansLeukocytesLyme DiseaseMiceMice, Inbred C57BLMice, KnockoutMyocarditisPhagocytosisReceptors, Urokinase Plasminogen ActivatorSkinStatistics, NonparametricUp-RegulationUrinary BladderUrokinase-Type Plasminogen ActivatorConceptsB. burgdorferi numbersWT controlsPhagocytotic capacityC3H/HeN backgroundIL-1beta mRNA expressionBorrelia burgdorferiB. burgdorferi infectionRole of uPARSevere carditisBurgdorferi infectionImmune responseLeukocyte functionSpirochete Borrelia burgdorferiFibrinolytic systemPAI-1Facilitate clearanceMRNA expressionHuman leukocytesLyme borreliosisMiceB. burgdorferiCausative agentProteinase receptorUPARAdequate eradication
2008
Salp15 Binding to DC-SIGN Inhibits Cytokine Expression by Impairing both Nucleosome Remodeling and mRNA Stabilization
Hovius JW, de Jong MA, Dunnen J, Litjens M, Fikrig E, van der Poll T, Gringhuis SI, Geijtenbeek TB. Salp15 Binding to DC-SIGN Inhibits Cytokine Expression by Impairing both Nucleosome Remodeling and mRNA Stabilization. PLOS Pathogens 2008, 4: e31. PMID: 18282094, PMCID: PMC2242833, DOI: 10.1371/journal.ppat.0040031.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBorrelia burgdorferiCell Adhesion MoleculesCells, CulturedCytokinesDendritic CellsDose-Response Relationship, DrugHumansIxodesLectins, C-TypeNucleosomesProtein BindingProto-Oncogene Proteins c-rafReceptors, Cell SurfaceRecombinant ProteinsRNA, MessengerSalivary Proteins and PeptidesToll-Like ReceptorsConceptsRaf-1B. burgdorferi infectionSerine/threonine kinase Raf-1Mitogen-activated protein kinase kinaseKinase Raf-1Post-transcriptional levelLyme diseaseProtein kinase kinaseRaf-1 activationBurgdorferi infectionDC-SIGNTNF-alpha mRNA stabilityHuman dendritic cell functionNucleosome remodelingTick salivary proteinsDendritic cell functionKinase kinasePro-inflammatory cytokinesAdaptive immune responsesToll-like receptorsMRNA stabilityMRNA stabilizationT cell activationMolecular mechanismsMajor vector
2002
Comparative 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 ehrlichiosis
2000
Arthropod- and Host-Specific Borrelia burgdorferi bbk32 Expression and the Inhibition of Spirochete Transmission
Fikrig E, Feng W, Barthold S, Telford S, Flavell R. Arthropod- and Host-Specific Borrelia burgdorferi bbk32 Expression and the Inhibition of Spirochete Transmission. The Journal Of Immunology 2000, 164: 5344-5351. PMID: 10799897, DOI: 10.4049/jimmunol.164.10.5344.Peer-Reviewed Original ResearchConceptsSpirochete transmissionLyme borreliosisB. burgdorferi infectionB. burgdorferi transmissionMechanisms of immunityIxodes scapularis ticksCutaneous sitesImmunized miceSpirochete numbersBurgdorferi infectionMurine infectionMurine hostMiceInfectionMRNA levelsScapularis ticksB. burgdorferiTick engorgementMurine tissuesVector-borne diseasesBorreliosisAdult ticksAntiserumBBK32Regulated expression
1998
Vaccination against Lyme Disease with Recombinant Borrelia burgdorferi Outer-Surface Lipoprotein A with Adjuvant
Steere A, Sikand V, Meurice F, Parenti D, Fikrig E, Schoen R, Nowakowski J, Schmid C, Laukamp S, Buscarino C, Krause D. Vaccination against Lyme Disease with Recombinant Borrelia burgdorferi Outer-Surface Lipoprotein A with Adjuvant. New England Journal Of Medicine 1998, 339: 209-215. PMID: 9673298, DOI: 10.1056/nejm199807233390401.Peer-Reviewed Original ResearchConceptsLyme diseaseSerologic testingVaccine efficacyAsymptomatic infectionLipoprotein AInjections of vaccineOuter surface lipoprotein AB. burgdorferi infectionFirst yearPlacebo recipientsPlacebo groupVaccine groupVaccine recipientsStudy entryRandomized trialsSystemic reactionsThird injectionBurgdorferi infectionEffective vaccineSkin lesionsReaction testingVaccineDefinite casesDiseaseInfection
1997
OspA antibodies inhibit the acquisition of Borrelia burgdorferi by Ixodes ticks
de Silva AM, Fish D, Burkot TR, Zhang Y, Fikrig E. OspA antibodies inhibit the acquisition of Borrelia burgdorferi by Ixodes ticks. Infection And Immunity 1997, 65: 3146-3150. PMID: 9234767, PMCID: PMC175444, DOI: 10.1128/iai.65.8.3146-3150.1997.Peer-Reviewed Original ResearchConceptsOspA antibodiesB. burgdorferiPassive antibody transferB. burgdorferi infectionIxodes ticksSurface protein ABurgdorferi-infected miceB. burgdorferi-infected miceLarval infection ratesOuter surface protein AAntibody transferAntibody responseBurgdorferi infectionInfection rateInfected ticksMiceInhibitory effectAntibodiesLarval infectionBorrelia burgdorferiBurgdorferiInfectionLarval ticksReservoir competenceSpirochetesLyme disease in transgenic mice expressing the Borrelia burgdorferi flagellin epitope implicated in human neuroborreliosis
Fikrig E, Barthold S. Lyme disease in transgenic mice expressing the Borrelia burgdorferi flagellin epitope implicated in human neuroborreliosis. FEMS Microbiology Letters 1997, 148: 137-143. PMID: 9084140, DOI: 10.1111/j.1574-6968.1997.tb10279.x.Peer-Reviewed Original ResearchConceptsTransgenic miceAntibody responseNervous systemNon-transgenic miceFlagellin epitopeTypes of miceB. burgdorferi infectionCentral nervous systemMyelin basic proteinBurgdorferi infectionNeurologic diseaseMyelinated regionsNeuroborreliosisLyme diseaseMiceNeural tissueBorrelia burgdorferiEpitopesFlagellin antibodyInfectionDiseaseBasic proteinCarditisArthritisFusion proteinTemporal pattern of Borrelia burgdorferi p21 expression in ticks and the mammalian host.
Das S, Barthold SW, Giles SS, Montgomery RR, Telford SR, Fikrig E. Temporal pattern of Borrelia burgdorferi p21 expression in ticks and the mammalian host. Journal Of Clinical Investigation 1997, 99: 987-995. PMID: 9062357, PMCID: PMC507907, DOI: 10.1172/jci119264.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibodies, BacterialAntigens, BacterialAntigens, SurfaceArthritis, InfectiousBacterial Outer Membrane ProteinsBacterial ProteinsBacterial VaccinesBorrelia burgdorferi GroupElectrophoresis, Gel, Pulsed-FieldEnzyme-Linked Immunosorbent AssayFemaleFlagellinFluorescent Antibody Technique, IndirectGene Expression Regulation, BacterialHumansImmunizationImmunization, PassiveImmunoblottingIxodesLipoproteinsLyme DiseaseMiceMice, Inbred C3HPlasmidsPolymerase Chain ReactionRecombinant ProteinsRNA, MessengerTime FactorsConceptsInfected miceHumoral responseLate-stage Lyme diseaseMarkers of infectionCourse of diseaseMurine Lyme borreliosisB. burgdorferiB. burgdorferi infectionHuman humoral responseIxodes dammini ticksBurgdorferi-infected miceLyme arthritisActive immunizationMammalian hostsPassive transferBurgdorferi infectionC3H miceMurine infectionDay 14P21 antibodyP21 expressionLyme borreliosisLyme diseaseMiceInfection
1996
Use of recombinant antigens of Borrelia burgdorferi in serologic tests for diagnosis of lyme borreliosis
Magnarelli LA, Fikrig E, Padula SJ, Anderson JF, Flavell RA. Use of recombinant antigens of Borrelia burgdorferi in serologic tests for diagnosis of lyme borreliosis. Journal Of Clinical Microbiology 1996, 34: 237-240. PMID: 8788993, PMCID: PMC228775, DOI: 10.1128/jcm.34.2.237-240.1996.Peer-Reviewed Original ResearchConceptsEnzyme-linked immunosorbent assaySerum samplesRecombinant antigensPolyvalent enzyme-linked immunosorbent assaysLyme borreliosisClass-specific enzyme-linked immunosorbent assaysWhole-cell B. burgdorferiImmunoglobulin M antibodiesB. burgdorferi infectionOspC antigenErythema migransRheumatoid arthritisM antibodiesBorrelia burgdorferi sensu strictoIgG antibodiesOral infectionSerologic testsBurgdorferi infectionBurgdorferi sensu strictoPredominant reactivityAntigenOuter surface proteins OspAImmunosorbent assayBorrelia burgdorferiB. burgdorferiBorrelia burgdorferi OspA is an arthropod-specific transmission-blocking Lyme disease vaccine.
de Silva AM, Telford SR, Brunet LR, Barthold SW, Fikrig E. Borrelia burgdorferi OspA is an arthropod-specific transmission-blocking Lyme disease vaccine. Journal Of Experimental Medicine 1996, 183: 271-275. PMID: 8551231, PMCID: PMC2192397, DOI: 10.1084/jem.183.1.271.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibodies, BacterialAntigens, BacterialAntigens, SurfaceArachnid VectorsBacterial Outer Membrane ProteinsBacterial VaccinesBorrelia burgdorferi GroupDigestive SystemFluorescent Antibody TechniqueImmunotherapy, AdoptiveIxodesLipoproteinsLyme DiseaseMiceMice, Inbred C3HSalivary GlandsConceptsOspA antibodiesTick attachmentUnfed nymphal ticksLyme disease vaccineB. burgdorferi infectionBlood mealMechanism of protectionTick blood mealSpirochete infectionBurgdorferi infectionDisease vaccineGland invasionExpression of OspAOuter surface proteinsSpirochetal agentLyme diseaseMiceSalivary gland invasionAntibodiesSalivary glandsBorrelia burgdorferiIxodes ticksOspA expressionTick gutVaccineP55, an immunogenic but nonprotective 55-kilodalton Borrelia burgdorferi protein in murine Lyme disease
Feng S, Barthold SW, Telford SR, Fikrig E. P55, an immunogenic but nonprotective 55-kilodalton Borrelia burgdorferi protein in murine Lyme disease. Infection And Immunity 1996, 64: 363-365. PMID: 8557366, PMCID: PMC173770, DOI: 10.1128/iai.64.1.363-365.1996.Peer-Reviewed Original ResearchConceptsProtective responseB. burgdorferi challengeMurine Lyme diseaseStrong antibody responseB. burgdorferi infectionBorrelia burgdorferi proteinsComplete Freund'sControl miceAntibody responseC3H miceBurgdorferi infectionImmunogenic antigensAnti-p55 antibodyLyme diseaseMiceP55B. burgdorferiInfectionAntigenResponseImmunizationFusion proteinTicksDiseaseFreund's