Molecular basis of heme scavenging by Gram-positive bacteria
革兰氏阳性菌清除血红素的分子基础
基本信息
- 批准号:10330038
- 负责人:
- 金额:$ 60.69万
- 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:2021-01-19 至 2026-12-31
- 项目状态:未结题
- 来源:
- 关键词:Actinobacteria classAffinityAntibioticsBacteriaBacterial Antibiotic ResistanceBasic ScienceBifidobacteriumBindingBiochemicalBiochemistryBiologyBloodCell Culture TechniquesCell WallCell surfaceCellsCellular MembraneChemicalsComplement 3d ReceptorsComplexCorynebacterium diphtheriaeCytoplasmDevelopmentDiphtheriaEnzymesErythrocytesEtiologyExcisionGoalsGram-Positive BacteriaHarvestHemeHeme IronHemoglobinHumanHuman bodyInfectionInfectious Skin DiseasesIronLearningLocationMass Spectrum AnalysisMediatingMembraneMetabolismMetalsMethodsMicrobeMicrobiologyMolecularMycobacterium tuberculosisNMR SpectroscopyNutritional ImmunityPathogenicityProcessProteinsProteomicsReporterResearchResearch PersonnelResearch Project GrantsStructural BiochemistrySurfaceSystemTestingUpper Respiratory InfectionsWorkX-Ray Crystallographycofactorexperimental studyextracellulargut microbiomegut microbiotahaptoglobin-hemoglobin complexheme receptorhuman pathogeninsightiron protoporphyrin IXmembermicrobialmodel organismnovelnovel therapeuticspathogenpathogenic bacteriaprotein functionreceptorsensorstructural biologytooluptake
项目摘要
Project Summary
Nearly all species of bacteria require iron to grow because it is an essential metal cofactor that is used by
microbial enzymes to mediate cellular metabolism. During infections, bacterial pathogens forage iron from
human hemoglobin (Hb) that is released from red blood cells, which contains ∼75–80% of the human body's
total iron content in the form of heme (iron protoporphyrin IX). The basic science studies outlined in this proposal
will determine how the human pathogen Corynebacterium diphtheriae acquires iron from Hb. This work will have
a broad impact, as C. diphtheriae is a model organism within the Actinobacteria phylum, which contains several
species of bacteria that are human pathogens, as well as microbes that are major components of the human
gastrointestinal microbiome. Research will be performed by an established team of investigators that have
complementary expertise in microbiology, proteomics, biochemistry and structural biology. We will determine
how microbial receptors capture Hb and remove its heme, and how cell wall embedded proteins ferry released
heme into the cell. In aim #1, we will determine how C. diphtheriae uses the HbpA receptor to capture Hb on the
cell surface and test the hypothesis that the receptor works in concert with surface associated heme-receptors
to distort Hb and trigger heme release. In aim #2, we will determine the molecular basis through which heme is
passed across the cell wall by determining how widely distributed Conserved Region (CR) domains in
Actinobacteria directly exchange heme by forming low-affinity transfer complexes. In aim #3, we will obtain a
systems-level understanding of the heme uptake process by applying mass spectrometry proteomics methods
to determine each component’s abundance and location, and by developing and applying a novel fluorogenic
Hb-reporter to track heme removal from Hb in cell culture. These studies will enable us to quantitatively assess
the importance of each system component in heme uptake, and to test the hypothesis that they form a molecular
wire through which heme flows to the membrane. The results of these studies will provide fundamental insight
into how C. diphtheriae and other Actinobacteria acquire heme-iron, and develop generalizable tools to study
this process in live bacteria. Combined, the results of this research could lead to new therapeutics to treat
infections caused by antibiotic resistant bacteria that work by disrupting heme import.
项目总结
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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{{ truncateString('Robert Thompson Clubb', 18)}}的其他基金
Bruker Avance III Console and QCI Cryoprobe for a 600 MHz NMR Spectrometer
用于 600 MHz NMR 波谱仪的 Bruker Avance III 控制台和 QCI 冷冻探针
- 批准号:
8640777 - 财政年份:2014
- 资助金额:
$ 60.69万 - 项目类别:
BRUKER 800 MHZ TCI CRYOPROBE: STRUCTURE/FUNCTION OF HIV-1 VPR
布鲁克 800 MHZ TCI 冷冻探针:HIV-1 VPR 的结构/功能
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7335201 - 财政年份:2006
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BRUKER 800 MHZ TCI CRYOPROBE: STRUCTURES AND DYNAMICS OF PROTEINS
BRUKER 800 MHZ TCI 冷冻探针:蛋白质的结构和动力学
- 批准号:
7335202 - 财政年份:2006
- 资助金额:
$ 60.69万 - 项目类别:
Cell Surface Protein Anchoring in Gram-positive Bacteria
革兰氏阳性细菌中的细胞表面蛋白锚定
- 批准号:
6888548 - 财政年份:2002
- 资助金额:
$ 60.69万 - 项目类别:
Cell Surface Protein Anchoring and Function in Gram-Positive Bacteria
革兰氏阳性细菌的细胞表面蛋白锚定和功能
- 批准号:
8437143 - 财政年份:2002
- 资助金额:
$ 60.69万 - 项目类别:
Cell Surface Protein Anchoring in Gram-Positive Bacteria
革兰氏阳性细菌中的细胞表面蛋白锚定
- 批准号:
7263369 - 财政年份:2002
- 资助金额:
$ 60.69万 - 项目类别:
Cell surface polymer display in Gram-positive bacteria
革兰氏阳性菌细胞表面聚合物展示
- 批准号:
9912688 - 财政年份:2002
- 资助金额:
$ 60.69万 - 项目类别:
Cell Surface Protein Anchoring in Gram-Positive Bacteria
革兰氏阳性细菌中的细胞表面蛋白锚定
- 批准号:
7767708 - 财政年份:2002
- 资助金额:
$ 60.69万 - 项目类别:
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