The role and fate of Mtb storage lipids LCTAG and MWE
Mtb 储存脂质 LCTAG 和 MWE 的作用和命运
基本信息
- 批准号:9893601
- 负责人:
- 金额:$ 24.41万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2020
- 资助国家:美国
- 起止时间:2020-03-23 至 2022-02-28
- 项目状态:已结题
- 来源:
- 关键词:AnabolismAntibiotic ResistanceBacteriaBiochemicalBiologicalBiological ProcessCarbonCause of DeathCell WallCommunicable DiseasesCytoplasmDataDiseaseDrug ToleranceEnergy-Generating ResourcesEnvironmentEstersExhibitsFailureFatty AcidsGenesGeneticGenus MycobacteriumGranulomaHomeostasisHypoxiaIn VitroLipidsMembraneMetabolicMetabolismMicrobial BiofilmsModelingMycobacterium tuberculosisNecrosisNutrientOrganismOxygenPathway interactionsPhasePhenotypePhysiologyProteinsRecyclingResearchResearch PersonnelResource SharingResourcesResuscitationRoleSourceStressSurfaceSystemTestingTriglyceridesTuberculosisUp-RegulationVirulenceWaxesbasecapsulecell envelopedeprivationesteraseexperimental studyextracellularhuman pathogenin vitro Modelin vivolatent infectionlipid transportmetabolomicsmutantmycobacterialmycolateresponsesuccesstargeted treatmenttranscriptome sequencingtuberculosis drugs
项目摘要
SUMMARY
Tuberculosis is one of the leading causes of death due to infectious disease despite the availability of anti-
tubercular drugs. The majority of M. tuberculosis (Mtb) infections result in latent TB where bacteria have
altered metabolism and exhibit phenotypic drug tolerance. The biological pathways used to maintain metabolic
homeostasis and then fuel resuscitation and replication are poorly understood.
A crucial component of dormancy or quiescence is the storage of carbon and energy sources in cell wall
lipids that can be recycled upon resuscitation. Mtb generates the “storage lipids” triacylglycerol (TAG) and wax
esters (WE) in late stationary phase and in response to stresses commonly associated with dormancy. During
the transition to active replication, it is believed that these lipids are mobilized and employed as a metabolic
resource. However, this has not been experimentally demonstrated. We recently described the Very Long-
Chain triacylglycerol (LCTAG) and mycolate wax ester (MWE) of Mtb. These lipids are exported from the
cytoplasm to the mycobacterial outer membrane or capsule by the MmpL11 transporter. The fates of LCTAG
and MWE once they are extracellular are not known. However, correct localization of LCTAG and MWE is
important for Mtb virulence and physiology since 1) MmpL11 is required for virulence and 2) the Mtb mmpL11
mutant has reduced resuscitation from an in vitro non-replicating persistence model. As storage lipids, surface-
localized LCTAG and MWE may be utilized as a shared resource to maintain viability and resuscitate from
non-replicating persistence.
Based on our data, we hypothesize that Mtb hydrolyzes, imports and utilizes exported storage lipids to
promote resuscitation from hypoxic and nutrient-restricted environments.
We propose to test this hypothesis by 1) Determining how LCTAG and MWE contribute to Mtb
resuscitation from non-replicating persistence, and 2) Define proteins involved in the LCTAG and MWE
biosynthesis and recycling pathway. This exploratory study combines unbiased approaches with genetic and
biochemical analyses to investigate the important biological process of Mtb cell envelope remodeling in
metabolism.
总结
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Georgiana E. Purdy其他文献
Cryo-EM structure of the emMycobacterium smegmatis/em MmpL5-AcpM complex
耻垢分枝杆菌 MmpL5-AcpM 复合物的冷冻电镜结构
- DOI:
10.1128/mbio.03035-24 - 发表时间:
2024-11-13 - 期刊:
- 影响因子:4.700
- 作者:
Rakesh Maharjan;Zhemin Zhang;Philip A. Klenotic;William D. Gregor;Georgiana E. Purdy;Edward W. Yu - 通讯作者:
Edward W. Yu
Mycobacterium tuberculosis and the four-minute phagosome
结核分枝杆菌和四分钟吞噬体
- DOI:
- 发表时间:
2005 - 期刊:
- 影响因子:0
- 作者:
D. Russell;Georgiana E. Purdy;R. Owens;K. Rohde;R. Yates - 通讯作者:
R. Yates
M. tuberculosis Rv2252 encodes a diacylglycerol kinase involved in the biosynthesis of phosphatidylinositol mannosides (PIMs)
结核分枝杆菌 Rv2252 编码参与磷脂酰肌醇甘露糖苷 (PIM) 生物合成的二酰甘油激酶
- DOI:
10.1111/j.1365-2958.2006.05174.x - 发表时间:
2006 - 期刊:
- 影响因子:3.6
- 作者:
Róisín M. Owens;F. Hsu;B. VanderVen;Georgiana E. Purdy;Elizabeth Hesteande;P. Giannakas;J. Sacchettini;J. Mckinney;P. Hill;J. Belisle;B. Butcher;Kevin Pethe;D. Russell - 通讯作者:
D. Russell
Georgiana E. Purdy的其他文献
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{{ truncateString('Georgiana E. Purdy', 18)}}的其他基金
Metabolite modulation of Mtb regulators of cell wall biogenesis
细胞壁生物发生的结核分枝杆菌调节剂的代谢调节
- 批准号:
10053297 - 财政年份:2016
- 资助金额:
$ 24.41万 - 项目类别:
Metabolite modulation of Mtb regulators of cell wall biogenesis
细胞壁生物发生的结核分枝杆菌调节剂的代谢调节
- 批准号:
9234364 - 财政年份:2016
- 资助金额:
$ 24.41万 - 项目类别:
Mtb regulators of essential and virulence-associated MmpLs
必需 MmpL 和毒力相关 MmpL 的 Mtb 调节因子
- 批准号:
9106596 - 财政年份:2015
- 资助金额:
$ 24.41万 - 项目类别:
TB Membrane Transporters and Intrinsic Resistance
结核病膜转运蛋白和固有耐药性
- 批准号:
8492015 - 财政年份:2011
- 资助金额:
$ 24.41万 - 项目类别:
TB Membrane Transporters and Intrinsic Resistance
结核病膜转运蛋白和固有耐药性
- 批准号:
8868006 - 财政年份:2011
- 资助金额:
$ 24.41万 - 项目类别:
TB Membrane Transporters and Intrinsic Resistance
结核病膜转运蛋白和固有耐药性
- 批准号:
8676638 - 财政年份:2011
- 资助金额:
$ 24.41万 - 项目类别:
TB Membrane Transporters and Intrinsic Resistance
结核病膜转运蛋白和固有耐药性
- 批准号:
8296272 - 财政年份:2011
- 资助金额:
$ 24.41万 - 项目类别:
TB Membrane Transporters and Intrinsic Resistance
结核病膜转运蛋白和固有耐药性
- 批准号:
8039513 - 财政年份:2011
- 资助金额:
$ 24.41万 - 项目类别:
Mycobacterial genes mediating resistance to bactericidal ubiquitin peptides
介导杀菌泛素肽抗性的分枝杆菌基因
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7514596 - 财政年份:2009
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