2024
Dual roles for a tick protein disulfide isomerase during the life cycle of the Lyme disease agent.
Tang X, Cui Y, Namarra U, Tian X, Rivas-Giorgi F, Fikrig E. Dual roles for a tick protein disulfide isomerase during the life cycle of the Lyme disease agent. MBio 2024, e0175424. PMID: 39470213, DOI: 10.1128/mbio.01754-24.Peer-Reviewed Original ResearchProtein disulfide isomeraseLyme disease agentDisulfide isomeraseBlood-feeding vectorsExtracellular pathogensGene expressionInvasion of host cellsThiol-disulfide oxidoreductasesDisease agentsGroup of enzymesStages of bacterial infectionVirulence factorsLife cycleChaperone activityMammalian hostsHost cellsBlood-feeding ticksIsomeraseMicrobial infectionsColonized ticksPathogensDiverse infectionsMicrobial invasionInfection of miceVector-borne diseasesAnopheles 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 agentsArthropodsAdiponectinReceptorsInfectionTransportersMealAdiponectin in the mammalian host influences ticks’ acquisition of the Lyme disease pathogen Borrelia
Tang X, Cao Y, Booth C, Arora G, Cui Y, Matias J, Fikrig E. Adiponectin in the mammalian host influences ticks’ acquisition of the Lyme disease pathogen Borrelia. PLOS Biology 2023, 21: e3002331. PMID: 37862360, PMCID: PMC10619873, DOI: 10.1371/journal.pbio.3002331.Peer-Reviewed Original ResearchConceptsAdipocyte-derived hormoneBite siteAdiponectin-deficient miceInfiltration of neutrophilsTick bite sitePro-inflammatory responseWild-type animalsIxodes scapularis ticksIL-1βVascular leakageHistamine releaseTick biteAdiponectinInfectious diseasesLyme disease agentBlood feeding arthropodsBorrelia burgdorferiScapularis ticksAnimal infectious diseasesBlood feedingB. burgdorferi survivalHuman bloodHormonePathogen acquisitionMammalian hostsDome1–JAK–STAT signaling between parasite and host integrates vector immunity and development
Rana V, Kitsou C, Dutta S, Ronzetti M, Zhang M, Bernard Q, Smith A, Tomás-Cortázar J, Yang X, Wu M, Kepple O, Li W, Dwyer J, Matias J, Baljinnyam B, Oliver J, Rajeevan N, Pedra J, Narasimhan S, Wang Y, Munderloh U, Fikrig E, Simeonov A, Anguita J, Pal U. Dome1–JAK–STAT signaling between parasite and host integrates vector immunity and development. Science 2023, 379: eabl3837. PMID: 36634189, PMCID: PMC10122270, DOI: 10.1126/science.abl3837.Peer-Reviewed Original ResearchConceptsBlood meal acquisitionMetazoan developmentTick receptorArthropod immunityMammalian hostsSignaling pathwaysReceptor motifEvolutionary dependenceVectorial competenceStem cellsCommunication pathwaysPathwayCritical roleVector immunityHostHigh affinityGenomeAntimicrobial componentsHedgehogJAKMotifMetamorphosisImmunityParasitesPhysiology
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
Aedes 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
Ixodes scapularis saliva components that elicit responses associated with acquired tick-resistance
Narasimhan S, Kurokawa C, Diktas H, Strank NO, Černý J, Murfin K, Cao Y, Lynn G, Trentleman J, Wu MJ, DePonte K, Kantor F, Anguita J, Hovius J, Fikrig E. Ixodes scapularis saliva components that elicit responses associated with acquired tick-resistance. Ticks And Tick-borne Diseases 2020, 11: 101369. PMID: 31924502, PMCID: PMC7382422, DOI: 10.1016/j.ttbdis.2019.101369.Peer-Reviewed Original ResearchConceptsTick-borne diseasesSalivary antigensAnti-tick vaccine candidatesIxodes scapularisTick salivary antigensTransmission of pathogensTick infestationTick rejectionTick proteinsViable vaccine targetsTick feedingPathogen transmissionRise worldTicksHost immune responseUrgent public health needScapularisMammalian hostsPathogensPublic health needsVaccine candidatesImmune responseSalivary glycoproteinsFeedingVaccine targeting
2013
Mosquito Saliva Serine Protease Enhances Dissemination of Dengue Virus into the Mammalian Host
Conway MJ, Watson AM, Colpitts TM, Dragovic SM, Li Z, Wang P, Feitosa F, Shepherd DT, Ryman KD, Klimstra WB, Anderson JF, Fikrig E. Mosquito Saliva Serine Protease Enhances Dissemination of Dengue Virus into the Mammalian Host. Journal Of Virology 2013, 88: 164-175. PMID: 24131723, PMCID: PMC3911723, DOI: 10.1128/jvi.02235-13.Peer-Reviewed Original ResearchConceptsDengue virusDENV infectivityAedes aegypti salivaMurine lymph nodesSalivary gland extractsAegypti salivaPrevention of diseaseLymph nodesMosquito salivaDENV loadVivo modelSerine protease activityNovel targetViral attachmentViral infectivityVirus infectivitySerine protease inhibitorHeparan sulfate proteoglycanExtracellular matrix proteinsRNA knockdownProtease inhibitorsInfectivitySulfate proteoglycanCell migrationMammalian hostsCharacterization 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 pathogensThe 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 ResearchConceptsComplex 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
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 hostsIxodes scapularis JAK-STAT Pathway Regulates Tick Antimicrobial Peptides, Thereby Controlling the Agent of Human Granulocytic Anaplasmosis
Liu L, Dai J, Zhao YO, Narasimhan S, Yang Y, Zhang L, Fikrig E. Ixodes scapularis JAK-STAT Pathway Regulates Tick Antimicrobial Peptides, Thereby Controlling the Agent of Human Granulocytic Anaplasmosis. The Journal Of Infectious Diseases 2012, 206: 1233-1241. PMID: 22859824, PMCID: PMC3448968, DOI: 10.1093/infdis/jis484.Peer-Reviewed Original ResearchConceptsJAK-STAT pathwayTick salivary glandsA. phagocytophilum infectionAntimicrobial peptidesElectrophoretic mobility shift assaysPeptide-encoding genesMobility shift assaysPhagocytophilum infectionHuman granulocytic anaplasmosisGene familyTransducer activatorMammalian hostsRNA interferenceShift assaysTranscription pathwayGene expressionJAK-STATJanus kinaseGranulocytic anaplasmosisSalivary glandsPathwayGenesCritical roleAnaplasma phagocytophilumKey roleActivation of the RpoN-RpoS regulatory pathway during the enzootic life cycle of Borrelia burgdorferi
Ouyang Z, Narasimhan S, Neelakanta G, Kumar M, Pal U, Fikrig E, Norgard MV. Activation of the RpoN-RpoS regulatory pathway during the enzootic life cycle of Borrelia burgdorferi. BMC Microbiology 2012, 12: 44. PMID: 22443136, PMCID: PMC3320556, DOI: 10.1186/1471-2180-12-44.Peer-Reviewed Original ResearchConceptsRpoN-RpoS regulatory pathwayRpoN-RpoS pathwayExpression of rpoSEnzootic life cycleMammalian infectionRegulatory pathwaysTranscription of rpoSOuter membrane lipoproteinLife cycleB. burgdorferiKey environmental stimuliLyme disease pathogenesisDiverse nichesMembrane lipoproteinMammalian hostsTarget genesTranscription levelsMicrobial survivalLipoprotein geneRpoSOrganism adaptationInfectious cycleFed larvaeIntermolt larvaeSustained transcriptionPostgenomic Analyses Reveal Development of Infectious Anaplasma phagocytophilum during Transmission from Ticks to Mice
Mastronunzio JE, Kurscheid S, Fikrig E. Postgenomic Analyses Reveal Development of Infectious Anaplasma phagocytophilum during Transmission from Ticks to Mice. Journal Of Bacteriology 2012, 194: 2238-2247. PMID: 22389475, PMCID: PMC3347074, DOI: 10.1128/jb.06791-11.Peer-Reviewed Original ResearchConceptsOpen reading frameA. phagocytophilum genomeObligate intracellular bacteriaBlood-feeding arthropodsCell surface proteinsMammalian cell cultureRickettsiales orderUncharacterized proteinsRibosomal proteinsEssential proteinsTranscriptome sequencingBacterial adaptationA. phagocytophilumDNA replicationTick salivary glandsPostgenomic analysisReading frameMammalian hostsAnaplasma phagocytophilumDevelopmental transitionsDC-specific markerIntracellular bacteriaTransmission feedingSurface proteinsProtein
2011
Innate immune control of West Nile virus infection
Arjona A, Wang P, Montgomery RR, Fikrig E. Innate immune control of West Nile virus infection. Cellular Microbiology 2011, 13: 1648-1658. PMID: 21790942, PMCID: PMC3196381, DOI: 10.1111/j.1462-5822.2011.01649.x.Peer-Reviewed Original ResearchConceptsWest Nile virusWNV infectionAntiviral innate immune mechanismsLong-term neurologic sequelaeWest Nile virus infectionRe-emerging zoonotic pathogenInnate immune controlInnate immune mechanismsLife-threatening meningoencephalitisInnate immune systemNeurologic sequelaeImmune controlInflammatory mediatorsImmune mechanismsMammalian hostsVirus infectionCurrent evidenceViral infectionAntiviral effectorsImmune systemFlaviviridae familyAntiviral mechanismInfectionNile virusJAK-STAT
2010
Lyme borreliosis vaccination: the facts, the challenge, the future
Schuijt TJ, Hovius JW, van der Poll T, van Dam AP, Fikrig E. Lyme borreliosis vaccination: the facts, the challenge, the future. Trends In Parasitology 2010, 27: 40-47. PMID: 20594913, DOI: 10.1016/j.pt.2010.06.006.Peer-Reviewed Original ResearchConceptsBorrelia burgdorferi sensu lato groupPrevalent arthropod-borne diseaseAnti-tick vaccinesLyme borreliosisArthropod-borne diseaseSensu lato groupTick proteinsTick vectorIxodes ticksNovel vaccination strategiesTicksMammalian hostsVaccination strategiesLyme diseaseVaccine candidatesBorreliosisBorrelia antigensVaccineAntigenDiseaseBorreliaOuter membrane proteinsWestern worldFuture candidatesSpirochetes
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
2007
Identification of Salp15 Homologues in Ixodes ricinus Ticks
Hovius JW, Ramamoorthi N, Veer C, de Groot KA, Nijhof AM, Jongejan F, van Dam AP, Fikrig E. Identification of Salp15 Homologues in Ixodes ricinus Ticks. Vector-Borne And Zoonotic Diseases 2007, 7: 296-303. PMID: 17896872, DOI: 10.1089/vbz.2006.0624.Peer-Reviewed Original ResearchConceptsSalp15 homologuesI. scapularis Salp15T cell activationDifferent Ixodes speciesAmino acid sequenceEntire amino acid sequenceSignal sequenceMammalian hostsProtein sequencesAcid sequenceC-terminusReverse transcriptase-polymerase chain reactionSensu strictoIxodes speciesSensu latoMajor vectorHomologuesB. burgdorferi sensu latoBorrelia speciesProteinSalp15Borrelia burgdorferi sensu strictoSpeciesI. ricinusBurgdorferi sensu strictoA Tick Antioxidant Facilitates the Lyme Disease Agent's Successful Migration from the Mammalian Host to the Arthropod Vector
Narasimhan S, Sukumaran B, Bozdogan U, Thomas V, Liang X, DePonte K, Marcantonio N, Koski RA, Anderson JF, Kantor F, Fikrig E. A Tick Antioxidant Facilitates the Lyme Disease Agent's Successful Migration from the Mammalian Host to the Arthropod Vector. Cell Host & Microbe 2007, 2: 7-18. PMID: 18005713, PMCID: PMC2699493, DOI: 10.1016/j.chom.2007.06.001.Peer-Reviewed Original ResearchConceptsMammalian hostsComplex feeding sitesLyme disease agent Borrelia burgdorferiSuccessful migrationMammalian responseTick Ixodes scapularisTick salivary glandsReactive oxygen speciesFeeding sitesArthropod vectorsTick proteinsBurgdorferi-infected miceOxygen speciesEfficient vectorCritical roleSpirochete acquisitionIxodes scapularisB. burgdorferiPathogensHostBorrelia burgdorferiI. scapularisInflammatory cellsImmune cellsSurvival advantage