grant
Chemical biology studies of MmpL3 inhibition and resistance in mycobacteria
Organization MICHIGAN STATE UNIVERSITYLocation EAST LANSING, UNITED STATESPosted 13 Jul 2023Deadline 30 Jun 2028
NIHUS FederalResearch GrantFY2025AcuteAirAmericanAntibiotic AgentsAntibiotic DrugsAntibioticsAntitubercular DrugsBenemycinBioavailabilityBiological AvailabilityBiologyCOPDCell BodyCellsCessation of lifeChemicalsChronic Obstruction Pulmonary DiseaseChronic Obstructive Lung DiseaseChronic Obstructive Pulmonary DiseaseCluster AnalysesCluster AnalysisCollectionCord FactorsCystic FibrosisDataDeathDevelopmentDiseaseDisorderDoseDrug KineticsDrug resistanceDrug resistance in MtbDrug resistance in Mycobacterium TuberculosisDrug resistant M TuberculosisDrug resistant MtbDrug resistant Mycobacteria TuberculosisDrugsEthambutolEvolutionExhibitsFrequenciesGeneralized GrowthGenus MycobacteriumGoalsGrowthHealthHigh Throughput AssayIn VitroIndividualInfectionIsonicotinic Acid HydrazideLibrariesLytotoxicityM . tuberculosis resistanceM abscessusM smegmatisM tbM tuberculosisM tuberculosis infectionM. abscessusM. smegmatisM. tbM. tb infectionM. tuberculosisM. tuberculosis infectionM.tb infectionM.tuberculosis infectionMTB infectionMacrophageMedicationMembrane Protein GeneMembrane ProteinsMembrane-Associated ProteinsMiceMice MammalsMicrosomesMiscellaneous AntibioticMissionModelingMtb drug resistanceMtb resistanceMucoviscidosisMurineMusMycobacteriumMycobacterium abscessusMycobacterium smegmatisMycobacterium tuberculosisMycobacterium tuberculosis (MTB) infectionMycobacterium tuberculosis infectionMycobacterium tuberculosis resistanceMycobacteroides abscessusMφNIAIDNTM infectionNational Institute of Allergy and Infectious DiseaseOralPharmaceutical PreparationsPharmacokineticsPhenotypePhysiologic AvailabilityPyrazinamidePyrazinecarboxamideResistanceResistance profileResistant profileRifadinRifampicinRifampinRimactaneSeriesSolubilityStructureStructure-Activity RelationshipSurface ProteinsTB drugsTB infectionTissue GrowthTrehaloseTrehalose DimycolatesTuberculosisUnited Statesanaloganti-TB drugsanti-tuberculosis drugsbactericidalbactericidechemical structure functionchronic obstructive pulmonary disordercommunicable disease transmissioncytotoxicitydesigndesigningdevelopmentaldisease transmissiondisseminated TBdisseminated tuberculosisdrug developmentdrug resistance M Tuberculosisdrug resistance Mycobacteria Tuberculosisdrug resistantdrug resistant M.tbdrug/agentefficacy studyexperimentexperimental researchexperimental studyexperimentsfitnessglobal healthhigh throughput screeningin vivoinfection due to Mycobacterium tuberculosisinfectious disease transmissioninhibitorinnovateinnovationinnovativeinterestisoniazidknock-downknockdownmouse modelmtbmurine modelmutantmycobacterialmycolatenon-tuberculosis mycobacterianon-tuberculosis mycobacterialnon-tuberculous mycobacterianon-tuberculous mycobacterialnon-tuberculous mycobacterial infectionnontuberculosis mycobacterialnontuberculous mycobacterianontuberculous mycobacterialnovelontogenyrational designresistance frequencyresistance in M . tuberculosisresistance in Mycobacterium tuberculosisresistance mechanismresistance mutationresistance strainresistance to Drugresistantresistant M . tuberculosisresistant Mtbresistant Mycobacterium tuberculosisresistant mechanismresistant mutationresistant strainresistant to Drugresponsescaffoldscaffoldingstandard of carestructure function relationshiptherapeutic targettooltuberculosis drugstuberculosis infectiontuberculous spondyloarthropathy
Description preview
MmpL3 (Mycobacterium membrane protein Large 3) is a common target of inhibitors of mycobacterial growth
identified by whole cell, phenotypic, high throughput screens. MmpL3 is a mycolate flippase that moves trehalose
monomycolate (TMM) to the pseudoperiplasmic space, from where TMM is modified to trehalose dimycolate
(TDM) and incorporated into…
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