2024
Bacterial 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, 1-14. 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. 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 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 ResearchA 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 hostsVaccinia Virus Strain MVA Expressing a Prefusion-Stabilized SARS-CoV-2 Spike Glycoprotein Induces Robust Protection and Prevents Brain Infection in Mouse and Hamster Models
Lorenzo M, Marín-López A, Chiem K, Jimenez-Cabello L, Ullah I, Utrilla-Trigo S, Calvo-Pinilla E, Lorenzo G, Moreno S, Ye C, Park J, Matía A, Brun A, Sánchez-Puig J, Nogales A, Mothes W, Uchil P, Kumar P, Ortego J, Fikrig E, Martinez-Sobrido L, Blasco R. Vaccinia Virus Strain MVA Expressing a Prefusion-Stabilized SARS-CoV-2 Spike Glycoprotein Induces Robust Protection and Prevents Brain Infection in Mouse and Hamster Models. Vaccines 2023, 11: 1006. PMID: 37243110, PMCID: PMC10220993, DOI: 10.3390/vaccines11051006.Peer-Reviewed Original ResearchVaccine candidatesStrong T cell responsesAngiotensin-converting enzyme 2Prime-boost regimensT cell responsesFull-length SARS-CoV-2 spike proteinEffective COVID-19 vaccineGolden Syrian hamstersSARS-CoV-2 spike glycoproteinSARS-CoV-2 spike proteinCOVID-19 vaccineRecombinant MVA vaccinesSARS-CoV-2S proteinBrain infectionMVA vaccinesCell-cell fusionAmino acid substitutionsVaccine platformHamster modelEnzyme 2Recombinant MVAVaccine vectorAnimal modelsRobust immunityCroquemort 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 activationCroquemortPancrustaceaHomologInsectsActivationCrustaceansKinaseFrankenbacteriosis targeting interactions between pathogen and symbiont to control infection in the tick vector
Mazuecos L, Alberdi P, Hernández-Jarguín A, Contreras M, Villar M, Cabezas-Cruz A, Simo L, González-García A, Díaz-Sánchez S, Neelakanta G, Bonnet S, Fikrig E, de la Fuente J. Frankenbacteriosis targeting interactions between pathogen and symbiont to control infection in the tick vector. IScience 2023, 26: 106697. PMID: 37168564, PMCID: PMC10165458, DOI: 10.1016/j.isci.2023.106697.Peer-Reviewed Original ResearchHuman granulocytic anaplasmosisPathogen infection/transmissionTick-borne pathogensTick-borne diseasesInfection/transmissionTick vectorGranulocytic anaplasmosisWildtype populationTick microbiotaPathogensModel pathogenTransovarialAnaplasmosisMSP4TicksAssociated reductionCompetitionLarvaeDisease riskParatransgenesisSymbiontsInfectionCommensal bacteriaBacteriaControlMalaria: influence of Anopheles mosquito saliva on Plasmodium infection
Arora G, Chuang Y, Sinnis P, Dimopoulos G, Fikrig E. Malaria: influence of Anopheles mosquito saliva on Plasmodium infection. Trends In Immunology 2023, 44: 256-265. PMID: 36964020, PMCID: PMC10074230, DOI: 10.1016/j.it.2023.02.005.Peer-Reviewed Original ResearchConceptsAnopheles salivaPlasmodium infectionInfected female mosquitoesMosquito salivary proteinsLocal host responseComponents of salivaMosquito salivaTherapeutic strategiesHost responsePlasmodium sporozoitesVector salivaPlasmodium protozoaBlood vesselsSalivaFemale mosquitoesBlood mealAnopheline mosquitoesInfectionMalariaVector-borne diseasesSkinHost-pathogen interactionsSporozoitesSalivary proteinsMosquitoesMosquito Salivary Proteins and Arbovirus Infection: From Viral Enhancers to Potential Targets for Vaccines
Marín-López A, Raduwan H, Chen T, Utrilla-Trigo S, Wolfhard D, Fikrig E. Mosquito Salivary Proteins and Arbovirus Infection: From Viral Enhancers to Potential Targets for Vaccines. Pathogens 2023, 12: 371. PMID: 36986293, PMCID: PMC10054260, DOI: 10.3390/pathogens12030371.Peer-Reviewed Original ResearchMosquito salivary proteinsImmune responseImportant public health challengeAdaptive immune responsesHost immune responsePublic health challengeNon-endemic areasSalivary proteinsSerious complicationsLicensed vaccineNeurological alterationsMosquito salivaClinical signsMosquito bitesHemorrhagic feverInfection outcomesRapid onsetArbovirus infectionExplosive outbreaksHealth challengesVaccineDifferent arbovirusesArboviral diseasesArthropod salivaPotential targetRepeated Tick Infestations Impair Borrelia burgdorferi Transmission in a Non-Human Primate Model of Tick Feeding
Narasimhan S, Booth C, Philipp M, Fikrig E, Embers M. Repeated Tick Infestations Impair Borrelia burgdorferi Transmission in a Non-Human Primate Model of Tick Feeding. Pathogens 2023, 12: 132. PMID: 36678479, PMCID: PMC9861725, DOI: 10.3390/pathogens12010132.Peer-Reviewed Original ResearchNon-human primatesImmune responseLyme diseaseTick transmissionAnimal modelsGuinea pigsNon-human primate modelProtective immune responseTick feedingTick infestationRobust immune responseTick salivary antigensElicit immune responsesHuman Lyme diseaseClinical manifestationsHuman pathogensPrimate modelSalivary antigensNon-natural hostsVaccine targetsDiseaseVaccine discoveryTick resistanceBorreliaNatural hostDome1–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