Project 1. Metabolic adaptations required for growth and virulence of Mtb at acidic pH.
Project 1. Metabolic adaptations required for growth and virulence of Mtb at acidic pH.
批准号:
10641874
负责人:
SABINE EHRT
金额:
$28.77万
依托单位国家:
美国
项目类别:
财政年份:
2020
资助国家:
美国
项目状态:
未结题
起止时间:
2020-06-12 至 2025-05-31
关键词:
AcidsAnabolismAntibiotic TherapyAutomobile DrivingBiochemicalBiologyCarbonCatabolismCell surfaceCellsCollaborationsComplexDataDefectDiseaseDyesEnzyme InteractionEnzymesExposure toFatty AcidsGene Expression ProfilingGenesGeneticGoalsGranulomaGrowthImmune responseImmunoprecipitationIn VitroInfectionInsertional MutagenesisLabelLipidsM. tuberculosis genomeMacrophageMapsMass Spectrum AnalysisMeasuresMetabolicMetabolic PathwayMetabolismMultienzyme ComplexesMycobacterium tuberculosisNatureNutritionalPathogenesisPathway AnalysisPathway interactionsPhagosomesPhasePropertyProteinsRegulationResistanceSignal TransductionSourceStainsStressStructureTestingTuberculosisVirulenceWorkacid stresscaseating granulomascell envelopeenzyme pathwayexperimental studyextracellularfatty acid metabolismgene inductionlipid biosynthesislipid metabolismmutantnext generation sequencingnovelprogramsresistance genetranscriptome sequencingtransmission process
中文摘要
项目1,摘要
英文摘要
Project 1, Abstract
Mycobacterium tuberculosis (Mtb) has to adapt to acidic niches inside the host, which include macrophages
phagosomes and the caseum of granulomas. Previous work led to the identification of acid resistance genes,
that enable Mtb to survive severe acid stress. The key pathways and underlying mechanisms that that enable
Mtb to adapt to and replicate in mildly acidic conditions, a requirement for its ability to transmit from one host to
another, are incompletely understood.
The central hypothesis driving this project is that exposure to acidic pH triggers a reprogramming of Mtb’s
metabolism towards lipid and fatty acid catabolism which facilitates growth and remodeling of its cell surface
lipids. We propose to (i) determine the importance of fatty acid and lipid metabolism from intra- and extracellular
stores for adaptation to and growth at acidic pH, (ii) determine the impact of acid pH on Mtb’s cell envelope
composition and define the importance of pH-dependent cell envelope remodeling for Mtb stress resistance and
(iii) define the genetic and physical structure of pathways required for Mtb’s adaptation to and growth at acidic
pH. These activities directly contribute to our overall program goal to understand key pathways in Mtb biology,
with a particular focus on complex pathways that are important for the adaptation to disease-relevant stress.
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
M. tuberculosis carbon metabolism during infection
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批准号:10716619
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项目类别:
-
资助金额:$65.23万
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财政年份:2023
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负责人:SABINE EHRT
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依托单位:
Tri-Institutional TRAC Basic Science Core
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批准号:10430741
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项目类别:
-
资助金额:$22.33万
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财政年份:2022
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负责人:SABINE EHRT
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依托单位:
Tri-Institutional TRAC Basic Science Core
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批准号:10675748
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项目类别:
-
资助金额:$18.39万
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财政年份:2022
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负责人:SABINE EHRT
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依托单位:
Turning Mycobacterium tuberculosis appetite for fatty acids against itself
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批准号:10592602
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项目类别:
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资助金额:$21.19万
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财政年份:2022
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负责人:SABINE EHRT
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依托单位:
Determinants of TB control, relapse and reinfection
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批准号:10268801
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项目类别:
-
资助金额:$275.55万
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财政年份:2021
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负责人:SABINE EHRT
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依托单位:
Determinants of TB control, relapse and reinfection
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批准号:10621299
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项目类别:
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资助金额:$256.5万
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财政年份:2021
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负责人:SABINE EHRT
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依托单位:
Admin Core
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批准号:10268802
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项目类别:
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资助金额:$14.12万
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财政年份:2021
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负责人:SABINE EHRT
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依托单位:
Determinants of Paucibacillary Mtb Infection in Mice
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批准号:10430228
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项目类别:
-
资助金额:$57.25万
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财政年份:2021
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负责人:SABINE EHRT
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依托单位:
Determinants of TB control, relapse and reinfection
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批准号:10430221
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项目类别:
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资助金额:$258.33万
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财政年份:2021
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负责人:SABINE EHRT
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依托单位:
Determinants of Paucibacillary Mtb Infection in Mice
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批准号:10621309
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项目类别:
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资助金额:$45.82万
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财政年份:2021
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负责人:SABINE EHRT
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依托单位:
Determinants of Paucibacillary Mtb Infection in Mice
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批准号:10268807
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项目类别:
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资助金额:$45.99万
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财政年份:2021
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负责人:SABINE EHRT
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依托单位:
Admin Core
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批准号:10430222
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项目类别:
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资助金额:$18.43万
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财政年份:2021
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负责人:SABINE EHRT
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依托单位:
Microbiome in TB treatment response and disease resolution
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批准号:10430225
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项目类别:
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资助金额:$49.94万
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财政年份:2021
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负责人:SABINE EHRT
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依托单位:
Microbiome in TB treatment response and disease resolution
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批准号:10268805
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项目类别:
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资助金额:$54.7万
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财政年份:2021
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负责人:SABINE EHRT
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依托单位:
Admin Core
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批准号:10621300
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项目类别:
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资助金额:$13.15万
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财政年份:2021
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负责人:SABINE EHRT
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依托单位:
Microbiome in TB treatment response and disease resolution
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批准号:10621304
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项目类别:
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资助金额:$48.48万
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财政年份:2021
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负责人:SABINE EHRT
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依托单位:
Project 1. Metabolic adaptations required for growth and virulence of Mtb at acidic pH.
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批准号:10426179
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项目类别:
-
资助金额:$29.28万
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财政年份:2020
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负责人:SABINE EHRT
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依托单位:
Core D. Administration Core
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批准号:10426175
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项目类别:
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资助金额:$6.34万
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财政年份:2020
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负责人:SABINE EHRT
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依托单位:
Project 4. Defining cell division pathways in Mtb.
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批准号:10641888
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项目类别:
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资助金额:$66.87万
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财政年份:2020
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负责人:SABINE EHRT
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依托单位:
Project 3. Defining the RNA processing and degradation pathways of Mtb.
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批准号:10426181
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项目类别:
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资助金额:$42.93万
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财政年份:2020
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负责人:SABINE EHRT
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依托单位:
海外基金