2024
An atlas of human vector-borne microbe interactions reveals pathogenicity mechanisms
Hart T, Sonnert N, Tang X, Chaurasia R, Allen P, Hunt J, Read C, Johnson E, Arora G, Dai Y, Cui Y, Chuang Y, Yu Q, Rahman M, Mendes M, Rolandelli A, Singh P, Tripathi A, Ben Mamoun C, Caimano M, Radolf J, Lin Y, Fingerle V, Margos G, Pal U, Johnson R, Pedra J, Azad A, Salje J, Dimopoulos G, Vinetz J, Carlyon J, Palm N, Fikrig E, Ring A. An atlas of human vector-borne microbe interactions reveals pathogenicity mechanisms. Cell 2024, 187: 4113-4127.e13. PMID: 38876107, DOI: 10.1016/j.cell.2024.05.023.Peer-Reviewed Original ResearchCell invasionHost-microbe interactionsArthropod-borne pathogensHost sensingMicrobe interactionsTranscriptional regulationLyme disease spirocheteMicrobial interactionsExtracellular proteinsMicrobial pathogenesisEpidermal growth factorTissue colonizationEnvironmental cuesBacterial selectivityIntracellular pathogensPutative interactionsNext-generation therapeuticsPathogensFunctional investigationsInteractomeVector-borne diseasesImmune evasionPathogenic mechanismsStrainUnmet medical need
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
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
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 ResearchConceptsReceptor-mediated signalingAdiponectin receptorsAdiponectinLyme disease agentLyme disease spirochetePhospholipid metabolismPhosphatidylserine synthase ITick gutReceptor-like proteinMammalian homeostasisArthropod vectorsDisease agentsRNAi assaysRNA interferenceAlternative pathwaySynthase IPathwayMetabolic pathwaysTicksInfection
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 ResearchConceptsComplex 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 discoveriesHostTicksArthropodsSpirochetes
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
2006
Borrelia burgdorferi Lacking BBK32, a Fibronectin-Binding Protein, Retains Full Pathogenicity
Li X, Liu X, Beck DS, Kantor FS, Fikrig E. Borrelia burgdorferi Lacking BBK32, a Fibronectin-Binding Protein, Retains Full Pathogenicity. Infection And Immunity 2006, 74: 3305-3313. PMID: 16714558, PMCID: PMC1479267, DOI: 10.1128/iai.02035-05.Peer-Reviewed Original ResearchConceptsB. burgdorferiFlat ticksB. burgdorferi proteinsTick biteSpirochete acquisitionLyme disease spirocheteAdverse effectsBorrelia burgdorferiFibronectin-binding proteinBurgdorferiFibronectin binding proteinMiceSpirochete life cycleLyme pathogenesisB. burgdorferi B31Mammalian hostsSyringe inoculationExpression profilesBBK32Surface lipoproteinsFibronectin bindingPathogenesisExpressionInfectionTemporal expression profiles
2005
Association of Linear Plasmid 28-1 with an Arthritic Phenotype of Borrelia burgdorferi
Xu Q, Seemanapalli SV, Lomax L, McShan K, Li X, Fikrig E, Liang FT. Association of Linear Plasmid 28-1 with an Arthritic Phenotype of Borrelia burgdorferi. Infection And Immunity 2005, 73: 7208-7215. PMID: 16239515, PMCID: PMC1273894, DOI: 10.1128/iai.73.11.7208-7215.2005.Peer-Reviewed Original ResearchConceptsSevere combined immunodeficiencyArthritic phenotypeLp28-1Linear plasmid 28Borrelia burgdorferiArthritic pathologySevere arthritisSpirochete burdenSCID miceJoint tissuesLoss of plasmidsCombined immunodeficiencyPlasmid content analysisLyme disease spirocheteInfectivity studiesPlasmid patternsDecreased infectivityVirulence factorsFurther studiesMiceBurgdorferiBacterial quantificationPathogenicity studiesTissuePhenotypeThe 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 Research
2004
Borrelia 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 disruptionBurgdorferiMiceEssential 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 ResearchConceptsLyme disease spirocheteTissue pathologyBb infectionHuman isolatesBorrelia burgdorferiEnzootic life cycleVirulent strainOspABBSpirochetes
2002
Molecular 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 inoculumPathogensDNA 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
1998
Immune Evasion by Tickborne and Host-Adapted Borrelia burgdorferi
de Silva A, Fikrig E, Hodzic E, Kantor F, Telford S, Barthold S. Immune Evasion by Tickborne and Host-Adapted Borrelia burgdorferi. The Journal Of Infectious Diseases 1998, 177: 395-400. PMID: 9466527, DOI: 10.1086/514200.Peer-Reviewed Original ResearchHeat shock protein 70 of the agent of human granulocytic ehrlichiosis binds to Borrelia burgdorferi antibodies.
Ijdo J, Zhang Y, Anderson M, Goldberg D, Fikrig E. Heat shock protein 70 of the agent of human granulocytic ehrlichiosis binds to Borrelia burgdorferi antibodies. MSphere 1998, 5: 118-20. PMID: 9455892, PMCID: PMC121403, DOI: 10.1128/cdli.5.1.118-120.1998.Peer-Reviewed Original ResearchConceptsHuman granulocytic ehrlichiosisEhrlichial antigenHSP-70Borrelia burgdorferi antibodiesSerologic test resultsHeat shock protein 70Shock protein 70Burgdorferi antibodiesPatient seraGranulocytic ehrlichiosisLyme diseaseFirst weekHeat shock proteinsLyme disease spirochetePrior exposureImmunoglobulin GProtein 70Immunoblot analysisAntigenShock proteinsSerumAntibodiesPatientsIllnessIgG