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 ResearchMeSH KeywordsAnimalsAntigens, SurfaceBacterial Outer Membrane ProteinsBacterial VaccinesBorrelia burgdorferiHumansIxodesLipoproteinsLyme DiseaseLyme Disease VaccinesVaccinationConceptsTransmission 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
Development of an mRNA-lipid nanoparticle vaccine against Lyme disease
Pine M, Arora G, Hart T, Bettini E, Gaudette B, Muramatsu H, Tombácz I, Kambayashi T, Tam Y, Brisson D, Allman D, Locci M, Weissman D, Fikrig E, Pardi N. Development of an mRNA-lipid nanoparticle vaccine against Lyme disease. Molecular Therapy 2023, 31: 2702-2714. PMID: 37533256, PMCID: PMC10492027, DOI: 10.1016/j.ymthe.2023.07.022.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigens, SurfaceBacterial Outer Membrane ProteinsCOVID-19COVID-19 VaccinesHumansLyme DiseaseMiceSARS-CoV-2ConceptsLyme diseaseImmune responseCell-mediated immune responsesLyme disease vaccinePotent immune responsesProtein subunit vaccinesSARS-CoV-2Surface protein AVector-borne infectious diseasesMRNA-LNP vaccineOuter surface protein ASingle immunizationProtective efficacyMRNA vaccinesClinical vaccinesDisease vaccineNanoparticle vaccineSubunit vaccineVaccine developmentVaccineBacterial infectionsMRNA-LNPInfectious diseasesDiseaseMRNA platform
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
2014
Anaplasma phagocytophilum surface protein AipA mediates invasion of mammalian host cells
Seidman D, Ojogun N, Walker NJ, Mastronunzio J, Kahlon A, Hebert KS, Karandashova S, Miller DP, Tegels BK, Marconi RT, Fikrig E, Borjesson DL, Carlyon JA. Anaplasma phagocytophilum surface protein AipA mediates invasion of mammalian host cells. Cellular Microbiology 2014, 16: 1133-1145. PMID: 24612118, PMCID: PMC4115035, DOI: 10.1111/cmi.12286.Peer-Reviewed Original ResearchConceptsGranulocytic anaplasmosisObligate intracellular bacteriumVivo infectionInfectionPhagocytophilum infectionTransmission feedingObligate intracellular pathogensInfected ticksIntracellular pathogensNon-phagocytic cellsIntracellular bacteriumHL-60 cellsHost cell invasionCell invasionAnaplasma phagocytophilumPeptide-specific antiserumOwn uptakeHost cellsAttractive targetInternalization stepMammalian cellsInvasion proteinsSurface proteinsCell morphotypesCells
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 ResearchMeSH KeywordsAnimalsBacterial Outer Membrane ProteinsBorrelia burgdorferiGene DeletionGene Expression ProfilingHost-Pathogen InteractionsImmunoprecipitationLipoproteinsLyme DiseaseMiceMice, Inbred C3HMicrobial ViabilityTicksConceptsComplex 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
Anaplasma phagocytophilum Asp14 Is an Invasin That Interacts with Mammalian Host Cells via Its C Terminus To Facilitate Infection
Kahlon A, Ojogun N, Ragland SA, Seidman D, Troese MJ, Ottens AK, Mastronunzio JE, Truchan HK, Walker NJ, Borjesson DL, Fikrig E, Carlyon JA. Anaplasma phagocytophilum Asp14 Is an Invasin That Interacts with Mammalian Host Cells via Its C Terminus To Facilitate Infection. Infection And Immunity 2012, 81: 65-79. PMID: 23071137, PMCID: PMC3536139, DOI: 10.1128/iai.00932-12.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnaplasma phagocytophilumAnimalsBacterial Outer Membrane ProteinsBinding SitesCell AdhesionCell Line, TumorEhrlichiaEhrlichiosisGene Expression Regulation, BacterialGlutathione TransferaseHL-60 CellsHumansMembrane GlycoproteinsMembrane ProteinsMiceMolecular Sequence DataProtein BindingProtein Structure, TertiaryProteomeSequence Analysis, ProteinTranscription, GeneticUp-RegulationConceptsMammalian host cellsHost cellsReticulate cellsOuter membrane protein candidatesSurface proteinsOuter membrane protein AMembrane protein AA. phagocytophilum-infected ticksObligate intracellular bacteriumA. phagocytophilumGlutathione S-transferaseTranscriptional profilingSurface proteomeC-terminusAffinity purificationFamily AnaplasmataceaeProtein candidatesSelective biotinylationCellular invasionAsp14Transmission feedingAmino acidsS-transferaseIntracellular bacteriumP-selectin glycoprotein ligand-1Anaplasma phagocytophilum Outer Membrane Protein A Interacts with Sialylated Glycoproteins To Promote Infection of Mammalian Host Cells
Ojogun N, Kahlon A, Ragland SA, Troese MJ, Mastronunzio JE, Walker NJ, VieBrock L, Thomas RJ, Borjesson DL, Fikrig E, Carlyon JA. Anaplasma phagocytophilum Outer Membrane Protein A Interacts with Sialylated Glycoproteins To Promote Infection of Mammalian Host Cells. Infection And Immunity 2012, 80: 3748-3760. PMID: 22907813, PMCID: PMC3486060, DOI: 10.1128/iai.00654-12.Peer-Reviewed Original ResearchMeSH KeywordsAdhesins, BacterialAnaplasma phagocytophilumAnimalsBacterial Outer Membrane ProteinsCHO CellsCricetinaeEhrlichiosisHL-60 CellsHumansMembrane GlycoproteinsMiceMice, Inbred C3HN-Acetylneuraminic AcidPeptidoglycanTicksConceptsMammalian host cellsHuman granulocytic anaplasmosisHost cellsHL-60 cellsA. phagocytophilum organismsExtracellular domainP-selectin glycoprotein-1Outer Membrane Protein ASialylated glycoproteinsA. phagocytophilum infectionA. phagocytophilum-infected ticksN-terminal regionMembrane protein AObligate intracellular bacteriumAmino acids 19HGA patientsPhagocytophilum infectionInfectionTransmission feedingGlutathione S-transferaseGranulocytic anaplasmosisIntracellular bacteriumGlycoprotein 1Anaplasma phagocytophilumA. phagocytophilum
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 ResearchMeSH KeywordsAnimalsBacterial Outer Membrane ProteinsBorrelia burgdorferiGastrointestinal TractHemolymphLipoproteinsLyme DiseaseMolecular Sequence DataMovementTicksConceptsLyme 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
Preferential Protection of Borrelia burgdorferi Sensu Stricto by a Salp 15 Homologue in Ixodes ricinus Saliva
Hovius JW, Schuijt TJ, de Groot KA, Roelofs JJ, Oei GA, Marquart JA, de Beer R, Veer C, van der Poll T, Ramamoorthi N, Fikrig E, van Dam AP. Preferential Protection of Borrelia burgdorferi Sensu Stricto by a Salp 15 Homologue in Ixodes ricinus Saliva. The Journal Of Infectious Diseases 2008, 198: 1189-1197. PMID: 18752445, PMCID: PMC4317250, DOI: 10.1086/591917.Peer-Reviewed Original ResearchConceptsAntibody-mediated killingB. burgdorferiB. afzeliiB. gariniiEnzyme-linked immunosorbent assaySole causative agentBorrelia burgdorferi sensu latoBorrelia speciesSevere carditisOuter surface protein CImmune miceControl miceBorrelia burgdorferi sensu strictoBurgdorferi sensu latoSurface protein CSurvival advantageBurgdorferi sensu strictoSolid-phase overlayLyme borreliosisImmunosorbent assayProtein CCausative agentIxodes ticksBurgdorferiMice
2007
Role of Outer Surface Protein D in the Borrelia burgdorferi Life Cycle
Li X, Neelakanta G, Liu X, Beck DS, Kantor FS, Fish D, Anderson JF, Fikrig E. Role of Outer Surface Protein D in the Borrelia burgdorferi Life Cycle. Infection And Immunity 2007, 75: 4237-4244. PMID: 17620358, PMCID: PMC1951184, DOI: 10.1128/iai.00632-07.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBacterial Outer Membrane ProteinsBorrelia burgdorferiDisease Models, AnimalFemaleGene Expression Regulation, BacterialHumansIxodesLyme DiseaseMiceMice, Inbred C3HMutationConceptsB. burgdorferiSecond blood mealMurine modelSpirochete transmissionB. burgdorferi persistenceLyme borreliosisMiceB. burgdorferi strainsProtein DI. scapularisTick gutBlood mealBurgdorferi strainsSpirochete life cycleBurgdorferiGut extractsIxodes scapularisB. burgdorferi infectivityThreefold decreaseHost-specific signalsScapularisTicksBorreliosisOuter 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
2005
The Lyme disease agent exploits a tick protein to infect the mammalian host
Ramamoorthi N, Narasimhan S, Pal U, Bao F, Yang XF, Fish D, Anguita J, Norgard MV, Kantor FS, Anderson JF, Koski RA, Fikrig E. The Lyme disease agent exploits a tick protein to infect the mammalian host. Nature 2005, 436: 573-577. PMID: 16049492, PMCID: PMC4306560, DOI: 10.1038/nature03812.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigens, BacterialBacterial Outer Membrane ProteinsBorrelia burgdorferiIxodesLyme DiseaseMiceMice, Inbred C3HProtein BindingRNA InterferenceRNA, MessengerSalivary GlandsSalivary Proteins and Peptides
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 Changes Its Surface Antigenic Expression in Response to Host Immune Responses
Liang FT, Yan J, Mbow ML, Sviat SL, Gilmore RD, Mamula M, Fikrig E. Borrelia burgdorferi Changes Its Surface Antigenic Expression in Response to Host Immune Responses. Infection And Immunity 2004, 72: 5759-5767. PMID: 15385475, PMCID: PMC517580, DOI: 10.1128/iai.72.10.5759-5767.2004.Peer-Reviewed Original ResearchConceptsSurface antigenic expressionAntigenic expressionImmune attackImmune responseSevere combined immunodeficiency miceHostile immune environmentVigorous immune responseB. burgdorferiCombined immunodeficiency miceHost immune responseOspC antibodiesOuter surface protein CImmune environmentDecorin-binding protein AImmunocompetent miceImmune conditionsImmunodeficiency miceSurface protein CImmune pressureVlsE expressionLyme disease spirocheteProtein CBorrelia burgdorferiOspC expressionMammalian infectionProtective Niche for Borrelia burgdorferi to Evade Humoral Immunity
Liang FT, Brown EL, Wang T, Iozzo RV, Fikrig E. Protective Niche for Borrelia burgdorferi to Evade Humoral Immunity. American Journal Of Pathology 2004, 165: 977-985. PMID: 15331421, PMCID: PMC1618599, DOI: 10.1016/s0002-9440(10)63359-7.Peer-Reviewed Original ResearchConceptsChronic infectionHumoral immunityProtective nicheB. burgdorferiDecorin expressionLower decorin expressionDecorin-deficient miceWild-type miceStrong immune responseDecorin-binding protein ASpirochete burdenUrinary bladderImmune responsePersistent infectionMurine infectionEarly infectionInfectionExtracellular microbesDbpA expressionLyme disease spirocheteBorrelia burgdorferiC expressionTargeted disruptionBurgdorferiMiceBorrelia 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, GeneticPreferential Presence of Decorin-Binding Protein B (BBA25) and BBA50 Antibodies in Cerebrospinal Fluid of Patients with Neurologic Lyme Disease
Fikrig E, Coyle PK, Schutzer SE, Chen M, Deng Z, Flavell RA. Preferential Presence of Decorin-Binding Protein B (BBA25) and BBA50 Antibodies in Cerebrospinal Fluid of Patients with Neurologic Lyme Disease. Journal Of Clinical Microbiology 2004, 42: 1243-1246. PMID: 15004083, PMCID: PMC356844, DOI: 10.1128/jcm.42.3.1243-1246.2004.Peer-Reviewed Original ResearchOspB Antibody Prevents Borrelia burgdorferi Colonization of Ixodes scapularis
Fikrig E, Pal U, Chen M, Anderson JF, Flavell RA. OspB Antibody Prevents Borrelia burgdorferi Colonization of Ixodes scapularis. Infection And Immunity 2004, 72: 1755-1759. PMID: 14977984, PMCID: PMC356050, DOI: 10.1128/iai.72.3.1755-1759.2004.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibodies, BacterialAntigens, BacterialArachnid VectorsBacterial AdhesionBacterial Outer Membrane ProteinsBorrelia burgdorferiDigestive SystemImmunoglobulin Fab FragmentsIxodesLyme DiseaseTrypsinEssential 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 ResearchMeSH KeywordsAnimalsAntigens, BacterialAntigens, SurfaceArthropod VectorsBacterial Outer Membrane ProteinsBacterial VaccinesBorrelia burgdorferiGene TargetingGenes, BacterialHumansIxodesLipoproteinsLyme DiseaseMutationZoonoses