2020
Albumin 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 ResearchMeSH KeywordsAlbuminsAnimalsGranulocyte-Macrophage Colony-Stimulating FactorImmunotherapyMiceMycobacterium tuberculosisTuberculosisConceptsTuberculosis 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