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 pathwaysTicksInfectionAedes aegypti SNAP and a calcium transporter ATPase influence dengue virus dissemination
Marin-Lopez A, Jiang J, Wang Y, Cao Y, MacNeil T, Hastings AK, Fikrig E. Aedes aegypti SNAP and a calcium transporter ATPase influence dengue virus dissemination. PLOS Neglected Tropical Diseases 2021, 15: e0009442. PMID: 34115766, PMCID: PMC8195420, DOI: 10.1371/journal.pntd.0009442.Peer-Reviewed Original ResearchConceptsSalivary gland proteinsSuccessful viral transmissionNew mammalian hostDengue virusWild habitatsHabitat expansionGland proteinsA. aegypti vectorMammalian hostsUbiquitous expressionDENV infectionGene expressionMosquito midgutProtein componentsATPase proteinVector proteinProteinSalivary glandsBlood mealViral cycleAedes aegypti mosquitoesSusceptible hostsAedes aegyptiMosquitoesHost
2020
An Ixodes scapularis Protein Disulfide Isomerase Contributes to Borrelia burgdorferi Colonization of the Vector
Cao Y, Rosen C, Arora G, Gupta A, Booth CJ, Murfin KE, Cerny J, Lopez A, Chuang YM, Tang X, Pal U, Ring A, Narasimhan S, Fikrig E. An Ixodes scapularis Protein Disulfide Isomerase Contributes to Borrelia burgdorferi Colonization of the Vector. Infection And Immunity 2020, 88: 10.1128/iai.00426-20. PMID: 32928964, PMCID: PMC7671890, DOI: 10.1128/iai.00426-20.Peer-Reviewed Original ResearchConceptsTick gutTick bite siteVector-host interfaceAbility of spirochetesProtein disulfide isomerase A3Infected vertebrate hostsInflammatory responseBite siteLyme diseaseVertebrate hostsGutTick proteinsAdditional targetsMiceSpirochete life cycleSpirochete survivalArthropod vectorsSpirochetesRNA interferenceIllnessTicks
2017
Modulation of the tick gut milieu by a secreted tick protein favors Borrelia burgdorferi colonization
Narasimhan S, Schuijt TJ, Abraham NM, Rajeevan N, Coumou J, Graham M, Robson A, Wu MJ, Daffre S, Hovius JW, Fikrig E. Modulation of the tick gut milieu by a secreted tick protein favors Borrelia burgdorferi colonization. Nature Communications 2017, 8: 184. PMID: 28775250, PMCID: PMC5543126, DOI: 10.1038/s41467-017-00208-0.Peer-Reviewed Original ResearchConceptsB. burgdorferi colonizationTick gutImmune responseRNA interference-mediated silencingGut microbiomeLyme disease agentBorrelia burgdorferiB. burgdorferiGutTick proteinsVivo resultsBurgdorferiPixRAbrogationTick Ixodes scapularisArthropod vectorsDisease agentsGut proteinsIxodes scapularisAlterationsGut genesMicrobiomeTick biologyMiceBacterial biofilm formation
2014
Innexin AGAP001476 Is Critical for Mediating Anti-Plasmodium Responses in Anopheles Mosquitoes
Li MW, Wang J, Zhao YO, Fikrig E. Innexin AGAP001476 Is Critical for Mediating Anti-Plasmodium Responses in Anopheles Mosquitoes. Journal Of Biological Chemistry 2014, 289: 24885-24897. PMID: 25035430, PMCID: PMC4155657, DOI: 10.1074/jbc.m114.554519.Peer-Reviewed Original ResearchConceptsAnti-Plasmodium responseToll pathwayInnate immune responseGap junction proteinIMD pathwaySignal transductionExtracellular communicationSimultaneous knockdownAnopheles gambiaeImmune responseMidgut epitheliumInhibitor studiesKnockdownPlasmodium falciparum infectionCactusBlood mealGap junctionsVitellogenin levelsOocyst numbersAnopheles mosquitoesJunction proteinsCritical rolePathwayMRNA levelsMosquitoes
2013
ELF4 is critical for induction of type I interferon and the host antiviral response
You F, Wang P, Yang L, Yang G, Zhao YO, Qian F, Walker W, Sutton R, Montgomery R, Lin R, Iwasaki A, Fikrig E. ELF4 is critical for induction of type I interferon and the host antiviral response. Nature Immunology 2013, 14: 1237-1246. PMID: 24185615, PMCID: PMC3939855, DOI: 10.1038/ni.2756.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell LineCells, CulturedDNA-Binding ProteinsHEK293 CellsHeLa CellsHost-Pathogen InteractionsHumansImmunoblottingInterferon Regulatory Factor-3Interferon Regulatory Factor-7Interferon-betaMembrane ProteinsMiceMice, Inbred C57BLMice, KnockoutMicroscopy, ConfocalProtein BindingReverse Transcriptase Polymerase Chain ReactionRNA InterferenceSignal TransductionSurvival AnalysisTranscription FactorsTranscriptional ActivationWest Nile FeverWest Nile virusUBXN1 Interferes with Rig-I-like Receptor-Mediated Antiviral Immune Response by Targeting MAVS
Wang P, Yang L, Cheng G, Yang G, Xu Z, You F, Sun Q, Lin R, Fikrig E, Sutton RE. UBXN1 Interferes with Rig-I-like Receptor-Mediated Antiviral Immune Response by Targeting MAVS. Cell Reports 2013, 3: 1057-1070. PMID: 23545497, PMCID: PMC3707122, DOI: 10.1016/j.celrep.2013.02.027.Peer-Reviewed Original ResearchConceptsAntiviral immune responseInnate immune responseImmune responseLike receptorsSystemic antiviral immune responsesVirus-induced innate immune responsesDengue virus infectionType I interferon responseI interferon responseRNA virusesVirus infectionViral infectionStrong inhibitory effectViral replicationVirus replicationInterferon responseRNA virus replicationInhibitory effectWest NileMAVSVesicular stomatitisInfectionAdaptor moleculeFamily membersReceptors
2012
Enhanced Survival of Plasmodium-Infected Mosquitoes during Starvation
Zhao YO, Kurscheid S, Zhang Y, Liu L, Zhang L, Loeliger K, Fikrig E. Enhanced Survival of Plasmodium-Infected Mosquitoes during Starvation. PLOS ONE 2012, 7: e40556. PMID: 22808193, PMCID: PMC3393683, DOI: 10.1371/journal.pone.0040556.Peer-Reviewed Original ResearchConceptsSurvival advantageInsulin-like signalingAbility of mosquitoesInsulin-like peptidesInfection altersUninfected mosquitoesOocyst developmentPlasmodium developmentEnhanced expressionInsect vectorsPeriods of starvationFitness costsEnhanced survivalVertebrate hostsMicroarray analysisCarbohydrate catabolismCause malariaPlasmodiumStarvationMosquitoes
2010
Anaplasma phagocytophilum induces actin phosphorylation to selectively regulate gene transcription in Ixodes scapularis ticks
Sultana H, Neelakanta G, Kantor FS, Malawista SE, Fish D, Montgomery RR, Fikrig E. Anaplasma phagocytophilum induces actin phosphorylation to selectively regulate gene transcription in Ixodes scapularis ticks. Journal Of Experimental Medicine 2010, 207: 1727-1743. PMID: 20660616, PMCID: PMC2916137, DOI: 10.1084/jem.20100276.Peer-Reviewed Original ResearchMeSH KeywordsActinsAnaplasma phagocytophilumAnimalsCell LineCell NucleusEnzyme InhibitorsGastrointestinal TractGene ExpressionGene Expression RegulationGTP-Binding Protein beta SubunitsGTP-Binding Protein gamma SubunitsInsect ProteinsIxodesP21-Activated KinasesPhosphatidylinositol 3-KinasesPhosphoinositide-3 Kinase InhibitorsPhosphorylationPromoter Regions, GeneticProtein BindingRNA InterferenceRNA Polymerase IISalivary GlandsSalivary Proteins and PeptidesSignal TransductionTATA-Box Binding ProteinTranscription, GeneticConceptsRNA polymerase IIActin phosphorylationTATA box-binding proteinNuclear G-actinPhosphorylation of actinP21-activated kinaseA. phagocytophilumA. phagocytophilum survivalTick cell linesIxodes scapularis ticksPolymerase IIPhosphorylated actinGene crucialGbetagamma subunitsGene transcriptionFilamentous actinAnaplasma phagocytophilumGene expressionBacterial acquisitionScapularis ticksPhosphorylationG-actinIntracellular pathogensMedical importanceActin
2008
RNA interference screen for human genes associated with West Nile virus infection
Krishnan MN, Ng A, Sukumaran B, Gilfoy FD, Uchil PD, Sultana H, Brass AL, Adametz R, Tsui M, Qian F, Montgomery RR, Lev S, Mason PW, Koski RA, Elledge SJ, Xavier RJ, Agaisse H, Fikrig E. RNA interference screen for human genes associated with West Nile virus infection. Nature 2008, 455: 242-245. PMID: 18690214, PMCID: PMC3136529, DOI: 10.1038/nature07207.Peer-Reviewed Original ResearchMeSH KeywordsComputational BiologyDengue VirusEndoplasmic ReticulumGene Expression ProfilingGenome, HumanHeLa CellsHIVHumansImmunityMonocarboxylic Acid TransportersMuscle ProteinsProtein BindingRNA InterferenceUbiquitinationUbiquitin-Protein LigasesVesiculovirusVirus ReplicationWest Nile FeverWest Nile virus
2007
Anaplasma phagocytophilum specifically induces tyrosine phosphorylation of ROCK1 during infection
Thomas V, Fikrig E. Anaplasma phagocytophilum specifically induces tyrosine phosphorylation of ROCK1 during infection. Cellular Microbiology 2007, 9: 1730-1737. PMID: 17346310, DOI: 10.1111/j.1462-5822.2007.00908.x.Peer-Reviewed Original ResearchConceptsAnaplasma phagocytophilumPSGL-1Non-antibiotic strategiesHuman granulocytic anaplasmosisA. phagocytophilum infectionA. phagocytophilum-infected cellsTick-borne agentsPolymorphonuclear leucocytesPromyelocytic cell linePhagocytophilum infectionObligate intracellular pathogensInfectionTyrosine phosphorylationIntracellular pathogensGranulocytic anaplasmosisCell linesROCK1SykPhagocytophilumPhosphorylationNeutrophilsLeucocytesAntibodiesRab 5 Is Required for the Cellular Entry of Dengue and West Nile Viruses
Krishnan MN, Sukumaran B, Pal U, Agaisse H, Murray JL, Hodge TW, Fikrig E. Rab 5 Is Required for the Cellular Entry of Dengue and West Nile Viruses. Journal Of Virology 2007, 81: 4881-4885. PMID: 17301152, PMCID: PMC1900185, DOI: 10.1128/jvi.02210-06.Peer-Reviewed Original Research
2006
Disruption of the salivary protein 14 in Ixodes scapularis nymphs and impact on pathogen acquisition.
Pedra JH, Narasimhan S, Deponte K, Marcantonio N, Kantor FS, Fikrig E. Disruption of the salivary protein 14 in Ixodes scapularis nymphs and impact on pathogen acquisition. American Journal Of Tropical Medicine And Hygiene 2006, 75: 677-82. PMID: 17038693, DOI: 10.4269/ajtmh.2006.75.677.Peer-Reviewed Original ResearchConceptsScapularis nymphsProtein 14Adult Ixodes scapularisIxodes scapularis nymphsI. scapularisBorrelia burgdorferiTick feedingI. scapularis nymphsB. burgdorferiFamily expressionEngorgement weightTick weightPhysiological rolePathogen acquisitionBurgdorferiIxodes scapularisRNA interferenceExpressionDifferent mechanismsFeedingScapularisAn Ixodes scapularis protein required for survival of Anaplasma phagocytophilum in tick salivary glands
Sukumaran B, Narasimhan S, Anderson JF, DePonte K, Marcantonio N, Krishnan MN, Fish D, Telford SR, Kantor FS, Fikrig E. An Ixodes scapularis protein required for survival of Anaplasma phagocytophilum in tick salivary glands. Journal Of Experimental Medicine 2006, 203: 1507-1517. PMID: 16717118, PMCID: PMC2118316, DOI: 10.1084/jem.20060208.Peer-Reviewed Original ResearchConceptsA. phagocytophilum-infected miceRNA interference-mediated silencingA. phagocytophilumTick salivary proteinsI. scapularis salivary glandsRickettsia-like pathogensTick salivary glandsMammalian hostsGenus RickettsiaAnaplasma phagocytophilumGene expressionSalivary glandsIntracellular organismsArthropodsSalivary proteinsPathogensProteinPhagocytophilumExpressionTicksHuman anaplasmosisSilencingGenesOrganismsAnaplasma
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 ResearchUse of RNA Interference to Prevent Lethal Murine West Nile Virus Infection
Bai F, Wang T, Pal U, Bao F, Gould LH, Fikrig E. Use of RNA Interference to Prevent Lethal Murine West Nile Virus Infection. The Journal Of Infectious Diseases 2005, 191: 1148-1154. PMID: 15747251, DOI: 10.1086/428507.Peer-Reviewed Original ResearchConceptsWest Nile virusNile virusWest Nile virus infectionWest Nile virus replicationInjection 24 hAdministration of siRNAsIntraperitoneal inoculumViral loadProphylactic useFatal encephalitisLethal infectionVirus infectionViral infectionVirus replicationPartial protectionInfectionVirusMicePresent studyRNA interferenceEncephalitisSiRNAsAdministration
2004
Disruption of Ixodes scapularis anticoagulation by using RNA interference
Narasimhan S, Montgomery RR, DePonte K, Tschudi C, Marcantonio N, Anderson JF, Sauer JR, Cappello M, Kantor FS, Fikrig E. Disruption of Ixodes scapularis anticoagulation by using RNA interference. Proceedings Of The National Academy Of Sciences Of The United States Of America 2004, 101: 1141-1146. PMID: 14745044, PMCID: PMC337020, DOI: 10.1073/pnas.0307669100.Peer-Reviewed Original ResearchConceptsAnti-factor Xa activityNumerous infectious diseasesIxodes scapularis ticksRNA interferenceMultiple anticoagulantsReduction of mRNAXa activityVaccine candidatesInfectious diseasesTick salivaAnticoagulantsBabesia microtiPhysiologic functionI. scapularis salivaSalivary glandsBorrelia burgdorferiTick feedingScapularis ticksAnticoagulant activityAnaplasma phagocytophilumTick engorgementSuch interventionsEngorgement weightEngorgementKey target