2024
The human CD47 checkpoint is targeted by an immunosuppressive Aedes aegypti salivary factor to enhance arboviral skin infectivity
Marin-Lopez A, Huck J, Esterly A, Azcutia V, Rosen C, Garcia-Milian R, Sefik E, Vidal-Pedrola G, Raduwan H, Chen T, Arora G, Halene S, Shaw A, Palm N, Flavell R, Parkos C, Thangamani S, Ring A, Fikrig E. The human CD47 checkpoint is targeted by an immunosuppressive Aedes aegypti salivary factor to enhance arboviral skin infectivity. Science Immunology 2024, 9: eadk9872. PMID: 39121194, DOI: 10.1126/sciimmunol.adk9872.Peer-Reviewed Original ResearchConceptsSuppress antiviral responsesArthropod proteinsPathogen replicationAntiviral responseProtein AVertebrate hostsMosquito salivary proteinsUp-regulatedBlood feedingHuman macrophagesPleomorphic effectsSkin infectionsZika virus disseminationInhibit proinflammatory responsesSalivary proteinsProteinNatural ligandWhite blood cellsHuman skin explantsProinflammatory responseMosquito salivaVirus disseminationHuman CD47Salivary factorsArbovirus infectionAnopheles gambiae lacking AgTRIO probe inefficiently on a mammalian host
Chuang Y, Dong Y, Stone H, Abouneameh S, Tang X, Raduwan H, Dimopoulos G, Fikrig E. Anopheles gambiae lacking AgTRIO probe inefficiently on a mammalian host. Cell Reports 2024, 43: 114600. PMID: 39126653, PMCID: PMC11407849, DOI: 10.1016/j.celrep.2024.114600.Peer-Reviewed Original ResearchVertebrate hostsAnopheles gambiaePlasmodium sporozoitesCRISPR-Cas9-mediated genome editingPlasmodium transmissionTransmit malariaMosquito probingMosquito salivaTransmit PlasmodiumBlood resourcesMalariaRepetitive probesBloodPlasmodiumMammalian hostsAbility of mosquitoesBlood mealGenome editingA. gambiaeKnockoutVertebratesGambiaHostMealSaliva
2023
Signaling between mammalian adiponectin and a mosquito adiponectin receptor reduces Plasmodium transmission
Chuang Y, Stone H, Abouneameh S, Tang X, Fikrig E. Signaling between mammalian adiponectin and a mosquito adiponectin receptor reduces Plasmodium transmission. MBio 2023, 15: e02257-23. PMID: 38078744, PMCID: PMC10790699, DOI: 10.1128/mbio.02257-23.Peer-Reviewed Original ResearchBlood mealComplex life cycleMosquito fitnessMammalian hostsMammalian adiponectinPathogen infectivityLipid transportersVertebrate hostsAdiponectin receptorsHematophagous arthropodsFemale mosquitoesPlasmodium transmissionLife cycleMosquitoesImportant lipid transporterPathwayHostInfectious agentsVector-borne infectious agentsArthropodsAdiponectinReceptorsInfectionTransportersMealA mosquito AgTRIO mRNA vaccine contributes to immunity against malaria
Chuang Y, Alameh M, Abouneameh S, Raduwan H, Ledizet M, Weissman D, Fikrig E. A mosquito AgTRIO mRNA vaccine contributes to immunity against malaria. Npj Vaccines 2023, 8: 88. PMID: 37286568, PMCID: PMC10244833, DOI: 10.1038/s41541-023-00679-x.Peer-Reviewed Original ResearchHumoral responseFuture malaria vaccinesMosquito saliva proteinsRobust humoral responseImmunization of miceVector antigensIsotype antibodiesIgG titersImmunized miceMalaria vaccinePassive immunizationIgG2a isotypesMRNA vaccinesPlasmodium infectionMosquito bitesMRNA lipid nanoparticlesVaccineMRNA-LNPPlasmodium sporozoitesMalariaMiceImmunizationSaliva proteinsPotential usefulnessVertebrate hosts
2022
Tick transmission of Borrelia burgdorferi to the murine host is not influenced by environmentally acquired midgut microbiota
Narasimhan S, Rajeevan N, Graham M, Wu MJ, DePonte K, Marion S, Masson O, O’Neal A, Pedra JHF, Sonenshine DE, Fikrig E. Tick transmission of Borrelia burgdorferi to the murine host is not influenced by environmentally acquired midgut microbiota. Microbiome 2022, 10: 173. PMID: 36253842, PMCID: PMC9575305, DOI: 10.1186/s40168-022-01378-w.Peer-Reviewed Original Research
2021
Immunomodulation by Mosquito Salivary Protein AgSAP Contributes to Early Host Infection by Plasmodium
Arora G, Sajid A, Chuang YM, Dong Y, Gupta A, Gambardella K, DePonte K, Almeras L, Dimopolous G, Fikrig E. Immunomodulation by Mosquito Salivary Protein AgSAP Contributes to Early Host Infection by Plasmodium. MBio 2021, 12: e03091-21. PMID: 34903042, PMCID: PMC8669493, DOI: 10.1128/mbio.03091-21.Peer-Reviewed Original ResearchConceptsLocal inflammatory responsePlasmodium berghei sporozoitesSalivary antigensInflammatory responseBerghei sporozoitesPlasmodium falciparumMosquito salivary proteinsPrevention of malariaLocal host responseAnopheline mosquitoesVertebrate hostsHost responseSaliva secretionVaccine developmentMalariaEpidemiological analysisGenerate antibodiesAntigenArthropod salivaDisease prevalenceInfectionSaliva componentsSporozoitesVector-borne diseasesDiseaseA Mosquito AgTRIO Monoclonal Antibody Reduces Early Plasmodium Infection of Mice
Chuang YM, Tang XD, Fikrig E. A Mosquito AgTRIO Monoclonal Antibody Reduces Early Plasmodium Infection of Mice. Infection And Immunity 2021, 90: e00359-21. PMID: 34724388, PMCID: PMC8788779, DOI: 10.1128/iai.00359-21.Peer-Reviewed Original ResearchConceptsMonoclonal antibodiesFuture malaria vaccinesInfection of miceIsotype monoclonal antibodyVector antigensProtective immunityPassive immunizationMalaria vaccinePlasmodium infectionPassive transferProtein monoclonal antibodySignificant protectionSynergistic protectionMiceInfectionAntibodiesFc regionAntiserumVertebrate hostsProtein TrioImmunizationVaccineMalariaAntigenImmunity
2020
The Effects of A Mosquito Salivary Protein on Sporozoite Traversal of Host Cells
Chuang YM, Agunbiade TA, Tang XD, Freudzon M, Almeras L, Fikrig E. The Effects of A Mosquito Salivary Protein on Sporozoite Traversal of Host Cells. The Journal Of Infectious Diseases 2020, 224: 544-553. PMID: 33306099, PMCID: PMC8328219, DOI: 10.1093/infdis/jiaa759.Peer-Reviewed Original ResearchConceptsPassive immunizationCell traversal activityMosquito saliva proteinsMosquito salivary proteinsMosquito salivaNeutrophil chemotaxisProtein monoclonal antibodyProtective effectSporozoite glidingSporozoite infectivitySporozoite traversalMonoclonal antibodiesHost skinAnopheles mosquitoesProtein 1ImmunizationBlood mealSporozoitesSalivaMiceHost cellsSaliva proteinsSalivary proteinsAntiserumVertebrate hostsInteractions 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 discoveriesHostTicksArthropodsSpirochetesAn 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
2019
Anopheles gambiae Lacking AgTRIO Inefficiently Transmits Plasmodium berghei to Mice
Chuang YM, Freudzon M, Yang J, Dong Y, Dimopoulos G, Fikrig E. Anopheles gambiae Lacking AgTRIO Inefficiently Transmits Plasmodium berghei to Mice. Infection And Immunity 2019, 87: 10.1128/iai.00326-19. PMID: 31285253, PMCID: PMC6704594, DOI: 10.1128/iai.00326-19.Peer-Reviewed Original ResearchConceptsBite siteControl mosquitoesMosquito salivary proteinsInfectivity of sporozoitesMosquito salivary glandsProinflammation cytokinesSporozoite infectionRNA interference-mediated silencingPlasmodium bergheiMiceSalivary glandsSporozoitesTNFExpression of genesMosquitoesSalivary proteinsBurdenExpressionVertebrate hostsSplenocytesCytokinesInfectionCell adhesionLiverBerghei
2018
Altered vector competence in an experimental mosquito-mouse transmission model of Zika infection
Uraki R, Hastings AK, Gloria-Soria A, Powell JR, Fikrig E. Altered vector competence in an experimental mosquito-mouse transmission model of Zika infection. PLOS Neglected Tropical Diseases 2018, 12: e0006350. PMID: 29505571, PMCID: PMC5854422, DOI: 10.1371/journal.pntd.0006350.Peer-Reviewed Original ResearchConceptsZIKV transmissionZika virus infectionNatural transmission routeInfected miceZIKV infectionZika infectionTesting vaccinesVirus infectionIntrathoracic injectionAnimal modelsZIKVInfectionMiceTransmission routesBlood mealVector competenceVector competencyMosquitoesTransmission modelVertebrate hostsMosquito modelPathogenesisVaccine
2013
Characterization of Ixophilin, A Thrombin Inhibitor from the Gut of Ixodes scapularis
Narasimhan S, Perez O, Mootien S, DePonte K, Koski RA, Fikrig E, Ledizet M. Characterization of Ixophilin, A Thrombin Inhibitor from the Gut of Ixodes scapularis. PLOS ONE 2013, 8: e68012. PMID: 23874485, PMCID: PMC3706618, DOI: 10.1371/journal.pone.0068012.Peer-Reviewed Original ResearchConceptsTick gutBlood mealVertebrate hostsTick gut proteinsPathogen transmissionBorrelia burgdorferi transmissionAnticoagulation strategiesThrombin inhibitory activityHemostatic mechanismThrombin inhibitorsMammalian coagulationIxodes scapularisMammalian hostsTick salivaLyme diseaseKey enzymeGut proteinsBorrelia burgdorferiTick feedingHost bloodHours of feedingGutFunctional suiteTick proteinsHuman pathogensAnopheles gambiae Circumsporozoite Protein–Binding Protein Facilitates Plasmodium Infection of Mosquito Salivary Glands
Wang J, Zhang Y, Zhao YO, Li MW, Zhang L, Dragovic S, Abraham NM, Fikrig E. Anopheles gambiae Circumsporozoite Protein–Binding Protein Facilitates Plasmodium Infection of Mosquito Salivary Glands. The Journal Of Infectious Diseases 2013, 208: 1161-1169. PMID: 23801601, PMCID: PMC3762383, DOI: 10.1093/infdis/jit284.Peer-Reviewed Original ResearchConceptsMosquito salivary glandsCircumsporozoite proteinSalivary glandsPlasmodium organismsPlasmodium circumsporozoite proteinMosquito-borne diseasePlasmodium life cycleSubstantial morbidityPlasmodium infectionMosquito bitesFed bloodGut wallPlasmodium sporozoitesSalivary gland proteinsPlasmodium speciesParasite loadGlandBlood mealInfectionGland proteinsVertebrate hostsVivo bioassaySporozoitesInvasionProtein
2012
Immunization with adenoviral-vectored tick salivary gland proteins (SALPs) in a murine model of Lyme borreliosis
Ullmann AJ, Dolan MC, Sackal CA, Fikrig E, Piesman J, Zeidner NS. Immunization with adenoviral-vectored tick salivary gland proteins (SALPs) in a murine model of Lyme borreliosis. Ticks And Tick-borne Diseases 2012, 4: 160-163. PMID: 23141105, PMCID: PMC4306421, DOI: 10.1016/j.ttbdis.2012.08.006.Peer-Reviewed Original ResearchConceptsTick salivary proteinsBorrelia burgdorferi infectionSalivary proteinsTick salivary gland proteinsSalivary gland proteinsTh1 responseImmunized miceSpecific immunityBurgdorferi infectionMurine modelSpirochete loadLyme borreliosisPrior exposureAdenovirus expression systemAdenoviral vectorTick challengeVaccinationMammalian hostsIxodes scapularisVertebrate hostsEnhanced 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
2011
A Tick Mannose-Binding Lectin Inhibitor Interferes with the Vertebrate Complement Cascade to Enhance Transmission of the Lyme Disease Agent
Schuijt TJ, Coumou J, Narasimhan S, Dai J, DePonte K, Wouters D, Brouwer M, Oei A, Roelofs JJ, van Dam AP, van der Poll T, Veer C, Hovius JW, Fikrig E. A Tick Mannose-Binding Lectin Inhibitor Interferes with the Vertebrate Complement Cascade to Enhance Transmission of the Lyme Disease Agent. Cell Host & Microbe 2011, 10: 136-146. PMID: 21843870, PMCID: PMC3170916, DOI: 10.1016/j.chom.2011.06.010.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsBorrelia burgdorferiCell Migration AssaysCloning, MolecularComplement Membrane Attack ComplexComplement Pathway, Mannose-Binding LectinFemaleGene SilencingHemolysisHumansImmunization, PassiveImmunotherapy, ActiveInsect ProteinsIxodesLarvaLyme DiseaseMiceMice, Inbred C3HMolecular Sequence DataNeutrophilsNymphPhagocytosisRabbitsRecombinant ProteinsSalivaSalivary Proteins and PeptidesSequence AlignmentConceptsComplement cascadeLyme disease agent Borrelia burgdorferiImpaired neutrophil phagocytosisTick salivary proteinsVector-borne pathogensLyme disease agentMammalian infectionVector colonizationVertebrate hostsTick midgutAlternative complement pathwayBorrelia transmissionComplement-mediated killingVector proteinNeutrophil phagocytosisEssential rolePathway inhibitorComplement pathwayDisease agentsSalivary proteinsBorrelia burgdorferiLectin inhibitorsProteinCascadeIxodes ticks
2008
A Differential Role for BB0365 in the Persistence of Borrelia burgdorferi in Mice and Ticks
Pal U, Dai J, Li X, Neelakanta G, Luo P, Kumar M, Wang P, Yang X, Anderson JF, Fikrig E. A Differential Role for BB0365 in the Persistence of Borrelia burgdorferi in Mice and Ticks. The Journal Of Infectious Diseases 2008, 197: 148-155. PMID: 18171298, DOI: 10.1086/523764.Peer-Reviewed Original ResearchConceptsVertebrate hostsWild-type B. burgdorferiArthropod vectorsB. burgdorferi persistenceB. burgdorferi transcriptomeDiverse murine tissuesSpirochete life cycleLife cycleB. burgdorferi B31Lyme disease agentGene productsMurine tissuesGenesWild rodentsDisease agentsDifferential rolesFeeding ticksB. burgdorferiInfectious isolatesHostBorrelia burgdorferiTicksTranscriptomePersistence of BorreliaMutants
2007
Tick–host–pathogen interactions in Lyme borreliosis
Hovius JW, van Dam AP, Fikrig E. Tick–host–pathogen interactions in Lyme borreliosis. Trends In Parasitology 2007, 23: 434-438. PMID: 17656156, DOI: 10.1016/j.pt.2007.07.001.Peer-Reviewed Original ResearchConceptsVertebrate hostsB. burgdorferi survivalB. burgdorferi genesEnzootic life cycleSpirochete survivalGene productsB. burgdorferiArthropod vectorsGenesVector moleculesLife cycleDifferent environmentsHostBorrelia burgdorferiIxodes ticksTROSPATicksSpirochetal agentBurgdorferiLyme borreliosisMicrobesSalp15ExpressionSurvival