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The impact of pyrazinamide on metabolism in Mycobacterium tuberculosis
Organization UNIVERSITY OF MINNESOTALocation MINNEAPOLIS, UNITED STATESPosted 10 Mar 2021Deadline 28 Feb 2026 β οΈ
NIHUS FederalResearch GrantFY2025AIDS/HIVActive OxygenAnimal ModelAnimal Models and Related StudiesAntitubercular DrugsAthymic MiceAthymic Nude MouseAutomobile DrivingBacillusCell BodyCell Communication and SignalingCell Mediated ImmunologyCell SignalingCell-Mediated ImmunityCellsCellular ImmunityChemosensitizationChemosensitization/PotentiationClinicalCoACoenzyme ACombined Modality TherapyCulture ProcedureDNA Molecular BiologyDNA mutationDevelopmentDiseaseDisorderDrug PrecursorsDrug resistance in MtbDrug resistance in Mycobacterium TuberculosisDrug resistant M TuberculosisDrug resistant MtbDrug resistant Mycobacteria TuberculosisDrug usageElementsEnvironmentEpistasisEpistatic DeviationExposure toGenesGenetic ChangeGenetic DiversityGenetic EpistasisGenetic VariationGenetic defectGenetic mutationGoalsHIV/AIDSHost FactorHost Factor ProteinHumanIFN-GammaIFN-gIFN-Ξ³IFNGIFNΞ³ImmuneImmune InterferonImmunesImmunityImpairmentIn VitroInfectionIntegration Host FactorsInteraction DeviationInterferon GammaInterferon Type IIIntermediary MetabolismIntracellular Communication and SignalingInvestigationKnowledgeLaboratory cultureM . tuberculosis resistanceM tbM tuberculosisM tuberculosis infectionM. tbM. tb infectionM. tuberculosisM. tuberculosis infectionM.tb infectionM.tuberculosis infectionMTB infectionMacrophageMediatingMetabolic ProcessesMetabolismMiceMice MammalsMicrobeModern ManMolecularMolecular BiologyMtb drug resistanceMtb resistanceMultimodal TherapyMultimodal TreatmentMurineMusMutationMycobacterium tuberculosisMycobacterium tuberculosis (MTB) infectionMycobacterium tuberculosis infectionMycobacterium tuberculosis resistanceMΟNude MiceNutrientO elementO2 elementOther GeneticsOxidative StressOxygenOxygen RadicalsPZA resistancePZA resistantPhenotypePopulationPotentiationPredispositionPro-DrugsPro-OxidantsProdrugsPyrazinamidePyrazinamide resistancePyrazinamide resistantPyrazinecarboxamideReactive Nitrogen SpeciesReactive Oxygen SpeciesRecombinantsRegimenRelapseResistanceResistance to PZAResistance to PyrazinamideResistant to PZAResistant to PyrazinamideRestRoleSignal TransductionSignal Transduction SystemsSignalingSusceptibilityT cell responseT-CellsT-LymphocyteTB drugsTB infectionTB therapyTB treatmentTherapeuticTreatment PeriodTuberculosisWild Type Mouseacylamidaseacylaseamidaseanti-TB drugsanti-microbialanti-tuberculosis drugsantimicrobialbiological adaptation to stressbiological signal transductioncell envelopecombination therapycombined modality treatmentcombined treatmentdevelopmentaldisseminated TBdisseminated tuberculosisdrivingdrug actiondrug discoverydrug resistance M Tuberculosisdrug resistance Mycobacteria Tuberculosisdrug resistant M.tbdrug useepistatic interactionepistatic relationshipgene x gene interactiongenetic epistasesgenome mutationimprovedin vivoinfection due to Mycobacterium tuberculosislFN-Gammaloss of function mutationmodel of animalmtbmulti-modal therapymulti-modal treatmentmutantmycobacterialnew approachesnovelnovel approachesnovel strategiesnovel strategypyrazine-2-carboxylic acidpyrazinecarboxylic acidpyrazinoic acidreaction; crisisresistance in M . tuberculosisresistance in Mycobacterium tuberculosisresistance mutationresistantresistant M . tuberculosisresistant Mtbresistant Mycobacterium tuberculosisresistant mutationresponsesmall moleculesocial rolestress responsestress; reactionstressorthymus derived lymphocytetreat M. tuberculosistreat Mtbtreat Mycobacterium tuberculosistreat tbtreat tuberculosistreatment daystreatment durationtuberculosis drugstuberculosis infectiontuberculosis therapytuberculosis treatmenttuberculous spondyloarthropathywildtype mouse
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Project Summary
Pyrazinamide (PZA) is a critical component of first-line tuberculosis (TB) therapy because it has dramatically
reduced relapse rates and treatment duration. PZA is weakly active in vitro, but potently sterilizing in vivo, due
to its outstanding activity against slow and non-replicating populations of Mycobacterium tuberculosis thatβ¦
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