Metabolic determinants of barrier function in rifampin-sensitive and -resistant Mtb
利福平敏感和耐药结核分枝杆菌屏障功能的代谢决定因素
基本信息
- 批准号:10612039
- 负责人:
- 金额:$ 47.81万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-07-01 至 2026-04-30
- 项目状态:未结题
- 来源:
- 关键词:AffectAnabolismAnti-Infective AgentsAntibiotic ResistanceAntimycobacterial AgentsBacteriaBacterial InfectionsBiologyCRISPR interferenceCell WallCell Wall AlterationCellsChemicalsCollaborationsComplexCrownsCytosolDNA-Directed RNA PolymeraseDataDrug resistance in tuberculosisEthambutolEvolutionExtreme drug resistant tuberculosisGoalsKnowledgeMeasuresMediatingMembrane LipidsMetabolicModelingModernizationMultidrug-Resistant TuberculosisMycobacterium tuberculosisOrganismPenetrationPeptidoglycanPermeabilityPharmaceutical PreparationsPharmacotherapyPhysiologicalPropertyRegulationResearchResearch PersonnelResistanceRifampinRoleStructureStructure-Activity RelationshipSystemTechnologyTherapeuticTuberculosisVancomycinVariantVirulenceWhole Organismacquired drug resistancearabinofuranosearabinogalactancell envelopechemotherapycombatcommon treatmentdrug actiondrug-sensitivegenome-wideimprovedindividualized medicineinnovationlenslipidomicsp-Aminosalicylic Acidprogramsresponsetooltuberculosis chemotherapytuberculosis drugstuberculosis treatmentvirtual
项目摘要
Project 2 - Metabolic determinants of barrier function in rifampin-sensitive and -resistant Mtb
Project Leader: Kyu Rhee
Co-investigator: Valerie Mizrahi
Collaborating investigators: Jeremy Rock (Core D), D. Branch Moody (Core B)
ABSTRACT
The overarching goal of this project is to elucidate specific cell envelope structure-activity relationships
mediating barrier function. A key and quite literal barrier to safer and simpler drugs and treatments for TB is its
highly unusual cell envelope. Improved knowledge of the barrier function of the Mtb envelope thus represents a
potential blueprint to developing better safer drugs. Unlike most bacteria, the Mycobacterium tuberculosis (Mtb)
envelope consists in a unique multilayered structure whose physico-chemical properties are widely believed to
mediate an intrinsic mechanism of antibiotic resistance. Using newly developed whole organism chemical
profiling and genome scale CRISPRi technologies, we challenge the longstanding view of Mtb cell wall as a
static and impermeant chemical barrier. Preliminary studies indicate that the Mtb cell envelope is chemically
selective, and its barrier activity is not a simple product of its bulk physico-chemical properties. These data
further show that both its composition and barrier function are dynamically regulated. This project specifically
focuses on Mtb barrier function through the therapeutic lens of the frontline TB drug rifampicin. We focus on
rifampicin because of its unique treatment shortening and sterilizing activities against drug-sensitive TB, and its
defining role in the biology of drug-resistant TB. In addition, because rifampicin has a single, well understood
target of action, the b subunit of RNA polymerase, which is located in the cytosol, it serves as a potential model
that could elucidate general principles that apply to any drug with cytosolic targets.
项目2 -利福平敏感和耐药结核分枝杆菌屏障功能的代谢决定因素
项目成果
期刊论文数量(0)
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专利数量(0)
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Kyu Y Rhee其他文献
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{{ truncateString('Kyu Y Rhee', 18)}}的其他基金
Metabolic determinants of barrier function in rifampin-sensitive and -resistant Mtb
利福平敏感和耐药结核分枝杆菌屏障功能的代谢决定因素
- 批准号:
10271485 - 财政年份:2021
- 资助金额:
$ 47.81万 - 项目类别:
Project 2: Essential metabolic objectives of M. tuberculosis aerobiology
项目2:结核分枝杆菌有氧生物学的基本代谢目标
- 批准号:
10190650 - 财政年份:2021
- 资助金额:
$ 47.81万 - 项目类别:
Project 2: Essential metabolic objectives of M. tuberculosis aerobiology
项目2:结核分枝杆菌有氧生物学的基本代谢目标
- 批准号:
10610922 - 财政年份:2021
- 资助金额:
$ 47.81万 - 项目类别:
Project 2: Essential metabolic objectives of M. tuberculosis aerobiology
项目2:结核分枝杆菌有氧生物学的基本代谢目标
- 批准号:
10404531 - 财政年份:2021
- 资助金额:
$ 47.81万 - 项目类别:
Metabolic determinants of barrier function in rifampin-sensitive and -resistant Mtb
利福平敏感和耐药结核分枝杆菌屏障功能的代谢决定因素
- 批准号:
10438918 - 财政年份:2021
- 资助金额:
$ 47.81万 - 项目类别:
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