Chemical Probes of Mycobacteria
分枝杆菌化学探针
基本信息
- 批准号:10595665
- 负责人:
- 金额:$ 57.93万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2017
- 资助国家:美国
- 起止时间:2017-02-01 至 2027-03-31
- 项目状态:未结题
- 来源:
- 关键词:Antibiotic TherapyAntibioticsAntimycobacterial AgentsArchitectureBiogenesisCOVID-19Cell WallCell divisionCellsCellular MorphologyChemicalsComplexDataDetectionDiseaseDrug resistanceEnvironmentGenerationsGenus MycobacteriumGoalsGrantGranulomaHumanImageImmuneImmune EvasionImmune systemInfectious AgentInvestigationKnowledgeLabelLinkLipidsLocationLungMacrophageMannoseMicrobeMonitorMycobacterium tuberculosisMycolic AcidNecrosisOsmosisPathogenicityPersonsPhenotypePolysaccharidesPredispositionProcessReactionReporterResearchResistanceRoleStressTimeTrehaloseTuberculosisVirulenceVisualizationanalogarabinofuranosearabinogalactancell envelopecell growthfluorophorefunctional groupimmunoregulationinsightlipoarabinomannanmycobacterialnovel strategiesnovel therapeuticsprogramsresistant strainresponsestemsugarthiosugartooluptake
项目摘要
Project Summary/Abstract Section
The rise of resistant strains of Mycobacterium tuberculosis (Mtb) demands new approaches to
combating this infectious agent. The survival of Mtb depends on the cell envelope, which is both
durable and dynamic. Mycobacteria modulate their cell envelope composition to subsist in the
harsh environments they encounter in the host. The proposed aims focus on developing new
tools to probe, perturb, and observe changes in the mycobacterial cell envelope. The focus of
Aim 1 is on visualizing arabinofuranose and mannose residues within the cell wall and the
immunomodulatory lipoarabinomannan (LAM). In Aim 2, we shall develop a complementary
probe that identifies methylthioxylofuranose (MTX)-capped LAM, a glycan that has been
detected in pathogenic mycobacteria. The probes generated in Aims 1 and 2 can reveal how cell
envelope composition varies under different conditions and between strains. In Aim 3, we shall
deploy a fluorogenic probe to visualize the changing mycobacterial cell envelope in real time.
This probe provides a means to explore phenotypic changes in the mycobacterial cell envelope
upon antibiotic treatment or uptake into macrophages. By pursuing the three aims, we expect to
uncover vulnerabilities in mycobacterial defenses that will lead to new antibiotic strategies.
Significance:
The overall objective of this application is to develop new chemical probes to understand how
the mycobacteria modify and maintain their cell envelope to survive under the extreme and
varied conditions they encounter in human hosts. We anticipate that this knowledge will
ultimately lead to the identification of new strategies to treat tuberculosis (TB).
项目概要/摘要部分
结核分枝杆菌(Mtb)耐药菌株的增加需要新的方法来解决
对抗这种传染性病原体。结核分枝杆菌的生存依赖于细胞包膜,这是两者兼而有之。
持久和动态。分枝杆菌调节它们的细胞被膜组成以在细胞膜中生存。
它们在宿主体内遇到的恶劣环境。新的目标集中在开发新的
探测、扰动和观察分枝杆菌细胞包膜变化的工具。的焦点
目的1是观察细胞壁内的阿拉伯呋喃糖和甘露糖残基,
免疫调节脂阿拉伯甘露聚糖(LAM)。在目标2中,我们将制定一项补充
一种识别甲硫基呋喃糖(MTX)封端的LAM的探针,
在致病分枝杆菌中检测到。目的1和2中产生的探针可以揭示细胞如何
包膜组成在不同条件下和菌株之间变化。在目标3中,
部署荧光探针以真实的实时观察变化的分枝杆菌细胞包膜。
这种探针提供了一种探索分枝杆菌细胞包膜表型变化的手段
在抗生素治疗或被巨噬细胞摄取后。通过实现这三个目标,我们希望
发现分枝杆菌防御系统的弱点,这将导致新的抗生素策略。
重要性:
本申请的总体目标是开发新的化学探针,以了解
分枝杆菌修改并维持它们的细胞包膜,以在极端环境下存活,
它们在人类宿主身上遇到的各种情况。我们预计,这些知识将
最终导致确定治疗结核病的新策略。
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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Laura L Kiessling其他文献
Laura L Kiessling的其他文献
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{{ truncateString('Laura L Kiessling', 18)}}的其他基金
Chemoenzymatic synthesis of bacterial polysaccharides
细菌多糖的化学酶法合成
- 批准号:
9981827 - 财政年份:2017
- 资助金额:
$ 57.93万 - 项目类别:
The Chemistry and Biology of Galactofuranose-Containing Glycans
含呋喃半乳糖聚糖的化学和生物学
- 批准号:
9528179 - 财政年份:2017
- 资助金额:
$ 57.93万 - 项目类别:
Chemoenzymatic synthesis of bacterial polysaccharides
细菌多糖的化学酶法合成
- 批准号:
9764158 - 财政年份:2017
- 资助金额:
$ 57.93万 - 项目类别:
TRAINING IN THE USE OF BRUKER AND VARIAN SPECTROMETERS AND NMR
布鲁克和瓦里安光谱仪和核磁共振的使用培训
- 批准号:
8361174 - 财政年份:2011
- 资助金额:
$ 57.93万 - 项目类别:
MECHANISTIC INVESTIGATION OF THE MYCOBACTERIAL GLYCOSYLTRANSFERASE GLFT2
分枝杆菌糖基转移酶 GLFT2 的机制研究
- 批准号:
8361170 - 财政年份:2011
- 资助金额:
$ 57.93万 - 项目类别:
MECHANISTIC INVESTIGATION OF THE MYCOBACTERIAL GLYCOSYLTRANSFERASE
分枝杆菌糖基转移酶的机制研究
- 批准号:
8168973 - 财政年份:2010
- 资助金额:
$ 57.93万 - 项目类别:
TRAINING IN THE USE OF BRUKER AND VARIAN SPECTROMETERS AND NMR
布鲁克和瓦里安光谱仪和核磁共振的使用培训
- 批准号:
8168978 - 财政年份:2010
- 资助金额:
$ 57.93万 - 项目类别:
Glycopeptides and Other Non-Natural Variants: Probes of Carbohydrate Function
糖肽和其他非天然变体:碳水化合物功能的探针
- 批准号:
7937468 - 财政年份:2009
- 资助金额:
$ 57.93万 - 项目类别:
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