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 proteinsAnopheles 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. gambiaeKnockoutVertebratesGambiaHostMealSalivamosGILT 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 infectionTranscriptomeOogenesisRegulatorProtein
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 hostsMalaria: 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 proteinsMosquitoes
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 diseasesDiseaseThe 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 pathwaysTicksInfectionA 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 hostsAn 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 interferenceIllnessTicksAlbumin fusion with granulocyte-macrophage colony-stimulating factor acts as an immunotherapy against chronic tuberculosis
Chuang YM, He L, Pinn ML, Tsai YC, Cheng MA, Farmer E, Karakousis PC, Hung CF. Albumin fusion with granulocyte-macrophage colony-stimulating factor acts as an immunotherapy against chronic tuberculosis. Cellular & Molecular Immunology 2020, 18: 2393-2401. PMID: 32382128, PMCID: PMC8484439, DOI: 10.1038/s41423-020-0439-2.Peer-Reviewed Original ResearchConceptsTuberculosis infectionChronic tuberculosis infectionPotent immune responsesGM-CSFLymph nodesDendritic cellsImmune responseChronic Mycobacterium tuberculosis infectionHigher IL-1β levelsAlbumin fusionLung bacillary burdenTB treatment regimensDendritic cell populationsDrug-resistant TBIL-1β levelsGM-CSF administrationMycobacterium tuberculosis infectionNaive T cellsIL-1β releaseBacillary burdenChronic tuberculosisNovel immunotherapiesTreatment regimensVaccination platformSubcutaneous administrationAntibiotic Treatment Shapes the Antigenic Environment During Chronic TB Infection, Offering Novel Targets for Therapeutic Vaccination
Chuang YM, Dutta NK, Gordy JT, Campodónico VL, Pinn ML, Markham RB, Hung CF, Karakousis PC. Antibiotic Treatment Shapes the Antigenic Environment During Chronic TB Infection, Offering Novel Targets for Therapeutic Vaccination. Frontiers In Immunology 2020, 11: 680. PMID: 32411131, PMCID: PMC7198710, DOI: 10.3389/fimmu.2020.00680.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigens, BacterialAntitubercular AgentsBacterial ProteinsCD4-Positive T-LymphocytesCD8-Positive T-LymphocytesCell LineChronic DiseaseDrug Resistance, BacterialFemaleGuanosine PentaphosphateGuinea PigsHydrolasesIsoniazidLigasesMacrophagesMiceMice, Inbred C57BLMycobacterium tuberculosisTreatment OutcomeTuberculosisTuberculosis VaccinesVaccinationVaccines, DNAConceptsTherapeutic vaccinationDNA vaccineT cellsC57BL/6 miceMtb persistersGuinea pigsAntigenic environmentFirst-line anti-TB drugsChronic TB infectionDrug-susceptible tuberculosisLung bacterial burdenAnti-TB drugsSpleens of miceHartley guinea pigsActivity of isoniazidAntitubercular treatmentReactive CD4Reactive CD8TB chemotherapyTB infectionTB treatmentCurrent regimenDaily dosesBacterial burdenIsoniazid treatment
2018
Intranasal Immunization with DnaK Protein Induces Protective Mucosal Immunity against Tuberculosis in CD4-Depleted Mice
Chuang YM, Pinn ML, Karakousis PC, Hung CF. Intranasal Immunization with DnaK Protein Induces Protective Mucosal Immunity against Tuberculosis in CD4-Depleted Mice. Frontiers In Cellular And Infection Microbiology 2018, 8: 31. PMID: 29473022, PMCID: PMC5809501, DOI: 10.3389/fcimb.2018.00031.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine TriphosphatasesAdministration, IntranasalAnimalsAntibodies, BacterialAntigens, BacterialBacterial ProteinsBCG VaccineCD4-Positive T-LymphocytesCross ReactionsCytokinesDisease Models, AnimalFemaleImmunity, MucosalImmunizationLymphocyte DepletionMiceMolecular ChaperonesMycobacterium tuberculosisNasal MucosaTuberculosisTuberculosis VaccinesConceptsBacillus Calmette-GuérinIntranasal vaccinationT cellsMucosal immunityProtective immunityVaccine candidatesTissue-resident CD4Different immune statusProtective mucosal immunityNew vaccine candidatesGlobal health challengeResident CD4BCG vaccinationIntranasal immunizationMtb infectionImmune statusImmunocompetent miceDNA vaccineBCG vaccineC57BL/6J miceCalmette-GuérinAvailable vaccinesImmunocompromised individualsLimited efficacyCD4
2016
Stringent Response Factors PPX1 and PPK2 Play an Important Role in Mycobacterium tuberculosis Metabolism, Biofilm Formation, and Sensitivity to Isoniazid In Vivo
Chuang YM, Dutta NK, Hung CF, Wu TC, Rubin H, Karakousis PC. Stringent Response Factors PPX1 and PPK2 Play an Important Role in Mycobacterium tuberculosis Metabolism, Biofilm Formation, and Sensitivity to Isoniazid In Vivo. Antimicrobial Agents And Chemotherapy 2016, 60: 6460-6470. PMID: 27527086, PMCID: PMC5075050, DOI: 10.1128/aac.01139-16.Peer-Reviewed Original ResearchMeSH KeywordsAcid Anhydride HydrolasesAnimalsAntitubercular AgentsBiofilmsCitric Acid CycleClofazimineDisease Models, AnimalDrug Resistance, BacterialGene ExpressionGlycerophosphatesIsoenzymesIsoniazidMeropenemMiceMycobacterium tuberculosisNaphthoquinonesPhosphotransferases (Phosphate Group Acceptor)PolyphosphatesThienamycinsTuberculosis VaccinesTuberculosis, Multidrug-ResistantVaccines, DNAXyloseConceptsM. tuberculosisVaccine-induced immunityGlobal health threatActivity of isoniazidMedical nonadherenceChronic tuberculosisProlonged therapyDNA vaccineAntibiotic treatmentMycobacterium tuberculosis metabolismReal-time PCRMurine modelM. tuberculosis metabolismAntibiotic toleranceLow intracellular levelsProtective activityAntibiotic sensitivityDrug resistanceTuberculosisLiquid chromatography-tandem mass spectrometryMycobacterium tuberculosisHealth threatKey regulatory moleculesChromatography-tandem mass spectrometryEnhanced susceptibility
2015
Deficiency of the Novel Exopolyphosphatase Rv1026/PPX2 Leads to Metabolic Downshift and Altered Cell Wall Permeability in Mycobacterium tuberculosis
Chuang YM, Bandyopadhyay N, Rifat D, Rubin H, Bader JS, Karakousis PC. Deficiency of the Novel Exopolyphosphatase Rv1026/PPX2 Leads to Metabolic Downshift and Altered Cell Wall Permeability in Mycobacterium tuberculosis. MBio 2015, 6: 10.1128/mbio.02428-14. PMID: 25784702, PMCID: PMC4453511, DOI: 10.1128/mbio.02428-14.Peer-Reviewed Original Research
2013
The Polyphosphate Kinase Gene ppk2 Is Required for Mycobacterium tuberculosis Inorganic Polyphosphate Regulation and Virulence
Chuang YM, Belchis DA, Karakousis PC. The Polyphosphate Kinase Gene ppk2 Is Required for Mycobacterium tuberculosis Inorganic Polyphosphate Regulation and Virulence. MBio 2013, 4: 10.1128/mbio.00039-13. PMID: 23695835, PMCID: PMC3663568, DOI: 10.1128/mbio.00039-13.Peer-Reviewed Original ResearchConceptsM. tuberculosis growthMIC of isoniazidFirst-line anti-TB drug isoniazidTuberculosis growthAnti-TB drug isoniazidAcute murine infectionLungs of miceJ774 macrophagesSuccessful human pathogenM. tuberculosis virulenceIL-12p70Lung CFUIL-10Immunobead assaysKey cytokineIL-9Interleukin-2Gamma interferonMurine modelLung macrophagesMurine infectionDay 7Control groupImmune systemMouse lung