2024
Two mosquito salivary antigens demonstrate promise as biomarkers of recent exposure to P. falciparum infected mosquito bites
Lapidus S, Goheen M, Sy M, Deme A, Ndiaye I, Diedhiou Y, Mbaye A, Hagadorn K, Sene S, Pouye M, Thiam L, Ba A, Guerra N, Mbengue A, Raduwan H, Gagnon J, Vigan-Womas I, Parikh S, Ko A, Ndiaye D, Fikrig E, Chuang Y, Bei A. Two mosquito salivary antigens demonstrate promise as biomarkers of recent exposure to P. falciparum infected mosquito bites. The Journal Of Infectious Diseases 2024, jiae525. PMID: 39475423, DOI: 10.1093/infdis/jiae525.Peer-Reviewed Original ResearchModerate transmission areasMosquito salivary proteinsModerately endemic areaAntibody responseMosquito exposureTransmission seasonP. falciparum infectionMalaria transmission seasonMalaria transmission intensityExposure to infectious mosquitoesMosquito bitesEntomological inoculation rateEndemic areasHuman immune responseInfected mosquito bitesTransmission areasDecline 3 monthsNo antibody responseExposure to infected mosquitoesP. falciparumControl cohortExposure to mosquitoesBead-based assayImmune responseSalivary proteinsDual 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 diseasesAedes aegypti adiponectin receptor-like protein signaling facilitates Zika virus infection
Chen T, Marín-López A, Raduwan H, Fikrig E. Aedes aegypti adiponectin receptor-like protein signaling facilitates Zika virus infection. MBio 2024, 15: e02433-24. PMID: 39373507, PMCID: PMC11559040, DOI: 10.1128/mbio.02433-24.Peer-Reviewed Original ResearchReceptor-like proteinZika virus infectionVirus infectionDevelopment of effective control strategiesSignificant public health challengeTranscriptome analysisTrypsin genesMetabolic pathwaysProtein signalingPublic health challengeViral infectionTransmission of viral diseasesAedes aegypti</i>InfectionBlood digestionZika virusProteinSignificance of signalsComplex interactionsVirusEffective control strategiesViral diseasesZikaMosquitoesPathwaySalp14 epitope-based mRNA vaccination induces early recognition of a tick bite
Cui Y, Cibichakravarthy B, Tang X, Alameh M, Dwivedi G, Weissman D, Fikrig E. Salp14 epitope-based mRNA vaccination induces early recognition of a tick bite. Vaccine 2024, 42: 126304. PMID: 39236403, PMCID: PMC11416896, DOI: 10.1016/j.vaccine.2024.126304.Peer-Reviewed Original ResearchTick bite siteGuinea pigsMRNA-LNPMRNA vaccinesBite siteImmunized guinea pigsTiters of IgGIxodes scapularis ticksDevelopment of erythemaLipid nanoparticlesSkin of guinea pigsI. scapularisTicksErythemaHistamine activityPigsTick bitesCarboxyl terminusRepeated exposureExposure of animalsAmino acidsSalivary proteinsVaccineMRNAGuineaVaccination to Prevent Lyme Disease: A Movement Towards Anti-Tick Approaches
Johnson E, Hart T, Fikrig E. Vaccination to Prevent Lyme Disease: A Movement Towards Anti-Tick Approaches. The Journal Of Infectious Diseases 2024, 230: s82-s86. PMID: 39140718, PMCID: PMC11322886, DOI: 10.1093/infdis/jiae202.Peer-Reviewed Original ResearchConceptsTransmission of tick-borne pathogensTick-borne pathogensIxodes spp ticksInhibited tick feedingTick feedingDisease vaccineTick vectorWildlife reservoirsOuter surface protein ALyme disease vaccineLyme diseaseTicksBorrelia burgdorferiLyme disease casesPreventing Lyme diseasePathogensFood and Drug AdministrationSurface protein AOspA-based vaccinesVaccineFeedingLymeProtein AFoodPrevent transmissionThe 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. gambiaeKnockoutVertebratesGambiaHostMealSalivaUBXN3B is crucial for B lymphopoiesis
Geng T, Yang D, Lin T, Harrison A, Wang B, Cao Z, Torrance B, Fan Z, Wang K, Wang Y, Yang L, Haynes L, Cheng G, Vella A, Flavell R, Pereira J, Fikrig E, Wang P. UBXN3B is crucial for B lymphopoiesis. EBioMedicine 2024, 106: 105248. PMID: 39018756, PMCID: PMC11287013, DOI: 10.1016/j.ebiom.2024.105248.Peer-Reviewed Original ResearchUbiquitin regulatory XPre-BCR signalingB cell receptorB lymphopoiesisKnockout miceValosin-containing proteinCaspase-3 protein levelsCell cycle arrestBone marrow transferNormal B lymphopoiesisUbiquitin ligaseIncreased viral loadCell-intrinsic mannerPathogenesis of severe acute respiratory syndrome coronavirus 2RNA sequencingCycle arrestDNA virusesCell survivalMarrow transferMultiple virusesSingle-cellImmunofluorescence microscopyViral loadMature BRespiratory virusesBacterial 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. scapularisPathogensZika virus exists in enterocytes and enteroendocrine cells of the Aedes aegypti midgut
Chen T, Raduwan H, Marín-López A, Cui Y, Fikrig E. Zika virus exists in enterocytes and enteroendocrine cells of the Aedes aegypti midgut. IScience 2024, 27: 110353. PMID: 39055935, PMCID: PMC11269924, DOI: 10.1016/j.isci.2024.110353.Peer-Reviewed Original ResearchAedes aegypti midgutEnteroendocrine cellsSingle-cell RNA sequencingIntestinal stem cellsVirus infectionPathogen interactionsExpressed genesRNA sequencingCopy numberTranscriptomic changesFunctional studiesInfected cellsZika virus infectionEnteroendocrineBlood digestionRNA copy numberCellular levelCell processesGenesMidgutPotential targetCell clustersCellsEnterocytesViral infectionAn 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 needmosGILT controls innate immunity and germ cell development in Anopheles gambiae
Arora G, Tang X, Cui Y, Yang J, Chuang Y, Joshi J, Sajid A, Dong Y, Cresswell P, Dimopoulos G, Fikrig E. mosGILT controls innate immunity and germ cell development in Anopheles gambiae. BMC Genomics 2024, 25: 42. PMID: 38191283, PMCID: PMC10775533, DOI: 10.1186/s12864-023-09887-0.Peer-Reviewed Original ResearchConceptsGerm cell developmentAnopheles gambiaeCell developmentOvarian developmentReductase-like proteinWild-type mosquitoesPlasmodium life cycleBiological controlGrowth genesEssential regulatorRNA sequencingA. gambiaeGenesGambiaeAltered expressionImpaired ovarian developmentMosquito vectorsLife cycleMosquitoesImmune activationPlasmodium infectionTranscriptomeOogenesisRegulatorProteinmRNA vaccination of rabbits alters the fecundity, but not the attachment, of adult Ixodes scapularis
Matias J, Cui Y, Lynn G, DePonte K, Mesquita E, Muramatsu H, Alameh M, Dwivedi G, Tam Y, Pardi N, Weissman D, Fikrig E. mRNA vaccination of rabbits alters the fecundity, but not the attachment, of adult Ixodes scapularis. Scientific Reports 2024, 14: 496. PMID: 38177212, PMCID: PMC10766947, DOI: 10.1038/s41598-023-50389-6.Peer-Reviewed Original Research
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 agentsArthropodsAdiponectinReceptorsInfectionTransportersMealMetabolomic changes associated with acquired resistance to Ixodes scapularis
Cui Y, Matias J, Tang X, Cibichakravarthy B, DePonte K, Wu M, Fikrig E. Metabolomic changes associated with acquired resistance to Ixodes scapularis. Ticks And Tick-borne Diseases 2023, 15: 102279. PMID: 37972499, DOI: 10.1016/j.ttbdis.2023.102279.Peer-Reviewed Original ResearchGuinea pigsHydroxyphenyllactic acidMetabolome of serumGroups of miceTyrosine metabolic pathwayTick biteImmune responseControl animalsIxodes scapularisTick salivaI. scapularisMiceInduction of componentsMetabolomic changesMortalityNitisinoneMolecular mechanismsAnimalsMetabolism pathwaysTyrosine degradationPigsTyrosine metabolism pathwayMetabolic pathwaysScapularisMetabolomeAdiponectin 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 hostsA ticking time bomb hidden in plain sight
Narasimhan S, Fish D, Pedra J, Pal U, Fikrig E. A ticking time bomb hidden in plain sight. Science Translational Medicine 2023, 15: eadi7829. PMID: 37851823, DOI: 10.1126/scitranslmed.adi7829.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsBulk and single-nucleus RNA sequencing highlight immune pathways induced in individuals during an Ixodes scapularis tick bite
Tang X, Lynn G, Cui Y, Cerny J, Arora G, Tomayko M, Craft J, Fikrig E. Bulk and single-nucleus RNA sequencing highlight immune pathways induced in individuals during an Ixodes scapularis tick bite. Infection And Immunity 2023, 91: e00282-23. PMID: 37846980, PMCID: PMC10652856, DOI: 10.1128/iai.00282-23.Peer-Reviewed Original ResearchConceptsRNA sequencingSingle-nucleus RNA sequencingBulk RNA sequencingInterleukin-17 signalingPlatelet activation pathwaysLaboratory guinea pigsSnRNA-seqHippo signalingIndividual genesPeripheral bloodTick biteAdaptive immunityAnti-tick vaccinesGuidance pathwayImmune pathwaysNew biomarkersHost responseGuinea pigsHematophagous arthropodsHost defenseCell adhesionTick attachmentNovel insightsTick feedingPhysiological consequencesDevelopment of an mRNA-lipid nanoparticle vaccine against Lyme disease
Pine M, Arora G, Hart T, Bettini E, Gaudette B, Muramatsu H, Tombácz I, Kambayashi T, Tam Y, Brisson D, Allman D, Locci M, Weissman D, Fikrig E, Pardi N. Development of an mRNA-lipid nanoparticle vaccine against Lyme disease. Molecular Therapy 2023, 31: 2702-2714. PMID: 37533256, PMCID: PMC10492027, DOI: 10.1016/j.ymthe.2023.07.022.Peer-Reviewed Original ResearchConceptsLyme diseaseImmune responseCell-mediated immune responsesLyme disease vaccinePotent immune responsesProtein subunit vaccinesSARS-CoV-2Surface protein AVector-borne infectious diseasesMRNA-LNP vaccineOuter surface protein ASingle immunizationProtective efficacyMRNA vaccinesClinical vaccinesDisease vaccineNanoparticle vaccineSubunit vaccineVaccine developmentVaccineBacterial infectionsMRNA-LNPInfectious diseasesDiseaseMRNA platformSpecific mRNA lipid nanoparticles and acquired resistance to ticks
Matias J, Cui Y, Tang X, Sajid A, Arora G, Wu M, DePonte K, Muramatsu H, Tam Y, Narasimhan S, Pardi N, Weissman D, Fikrig E. Specific mRNA lipid nanoparticles and acquired resistance to ticks. Vaccine 2023, 41: 4996-5002. PMID: 37407406, PMCID: PMC10530371, DOI: 10.1016/j.vaccine.2023.06.081.Peer-Reviewed Original Research