2024
Bacterial reprogramming of tick metabolism impacts vector fitness and susceptibility to infection
Samaddar S, Rolandelli A, O’Neal A, Laukaitis-Yousey H, Marnin L, Singh N, Wang X, Butler L, Rangghran P, Kitsou C, Cabrera Paz F, Valencia L, R. Ferraz C, Munderloh U, Khoo B, Cull B, Rosche K, Shaw D, Oliver J, Narasimhan S, Fikrig E, Pal U, Fiskum G, Polster B, Pedra J. Bacterial reprogramming of tick metabolism impacts vector fitness and susceptibility to infection. Nature Microbiology 2024, 9: 2278-2291. PMID: 38997520, DOI: 10.1038/s41564-024-01756-0.Peer-Reviewed Original ResearchMetabolic reprogrammingInfection of tick cellsInvestigate metabolic reprogrammingTick cellsLyme disease spirochete Borrelia burgdorferiSusceptibility to infectionArthropod-borne pathogensMetabolomics approachRickettsia buchneriHuman pathogensMetabolite allocationDiminished survivalBacterium Anaplasma phagocytophilumSpirochete Borrelia burgdorferiAcid metabolismA. phagocytophilum infectionInterspecies relationshipsElevated levelsInfectionFeeding impairmentHuman granulocytic anaplasmosisMetabolic responseArthropod vectorsI. scapularisPathogens
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
2017
Infection-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
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
2009
The 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
1997
Borrelia burgdorferi strain-specific Osp C-mediated immunity in mice
Bockenstedt LK, Hodzic E, Feng S, Bourrel KW, de Silva A, Montgomery RR, Fikrig E, Radolf JD, Barthold SW. Borrelia burgdorferi strain-specific Osp C-mediated immunity in mice. Infection And Immunity 1997, 65: 4661-4667. PMID: 9353047, PMCID: PMC175668, DOI: 10.1128/iai.65.11.4661-4667.1997.Peer-Reviewed Original ResearchConceptsChallenge infectionC antiserumImmunization studiesStrain-specific immunityAntibody-mediated immunityPassive immunization studiesImmune mouse serumSurface protein AOuter surface protein ADisease regressionInfected miceBorreliacidal activityC antibodySpirochete Borrelia burgdorferiAnimal modelsImmune serumMouse serumInfectionLyme borreliosisMiceHyperimmune serumOsp AImmunofluorescence studiesBorrelia burgdorferiSurface expressionBorrelia burgdorferi genes selectively expressed in ticks and mammals
de Silva AM, Fikrig E. Borrelia burgdorferi genes selectively expressed in ticks and mammals. Trends In Parasitology 1997, 13: 267-270. PMID: 15275064, DOI: 10.1016/s0169-4758(97)01074-0.Peer-Reviewed Original ResearchLyme disease vaccineTick-borne infectionsDisease vaccineHuman trialsSpirochete Borrelia burgdorferiDifferent surface proteinsLyme diseaseBorrelia burgdorferiLyme disease bacteriumBorrelia burgdorferi genesDisease bacteriumSurface proteinsRecent studiesDifferential gene expressionLife styleGene expressionVaccineInfectionDisease
1996
Identification of a Borrelia burgdorferi OspA T cell epitope that promotes anti-OspA IgG in mice.
Bockenstedt LK, Fikrig E, Barthold SW, Flavell RA, Kantor FS. Identification of a Borrelia burgdorferi OspA T cell epitope that promotes anti-OspA IgG in mice. The Journal Of Immunology 1996, 157: 5496-502. PMID: 8955199, DOI: 10.4049/jimmunol.157.12.5496.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsAntibodies, BacterialAntigens, BacterialAntigens, SurfaceBacterial Outer Membrane ProteinsBacterial VaccinesEpitope MappingFemaleImmunization, PassiveImmunoglobulin GInterleukin-4LipoproteinsLymphocyte ActivationMiceMice, Inbred C3HMolecular Sequence DataPeptidesT-LymphocytesVaccines, SyntheticConceptsT cell epitopesCell epitopesPhase III efficacy studiesTick-borne spirochete Borrelia burgdorferiTreatment-resistant Lyme arthritisT cell responsesSurface protein AB-cell epitopesOuter surface protein ALyme arthritisChallenge infectionIgG productionN-terminal epitopeT cellsMultisystem disorderMurine modelSpirochete Borrelia burgdorferiSubunit vaccineEfficacy studiesCell responsesRecombinant vaccineLyme borreliosisLyme diseaseInfectionBorrelia burgdorferi
1993
Protective immunity in lyme borreliosis
Fikrig E, Kantor FS, Barthold SW, Flavell RA. Protective immunity in lyme borreliosis. Trends In Parasitology 1993, 9: 129-131. PMID: 15463734, DOI: 10.1016/0169-4758(93)90176-g.Peer-Reviewed Original ResearchLyme diseaseCommon vector-borne illnessLyme borreliosisVector-borne illnessInitial diagnosisProtective immunityLate diseaseMurine modelSpirochete Borrelia burgdorferiVaccine candidatesSurface antigenEarly infectionDiseaseBorrelia burgdorferiBorreliosisTherapyVaccineIllnessInfectionAntigenDiagnosisImmunity