Mass Spectrometric Characterization of Lipopolysaccharides

脂多糖的质谱表征

基本信息

  • 批准号:
    8902209
  • 负责人:
  • 金额:
    $ 27.87万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2012
  • 资助国家:
    美国
  • 起止时间:
    2012-09-18 至 2016-08-31
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): Gram-negative bacteria are responsible for some of the deadliest and more widespread pandemics in the world. Helicobacter pylori is now recognized as the primary cause of peptic ulcer disease and gastric cancer, Camphorbacter jejuni and Vibrio cholera remain among the most common causes of diarrheal illness, and Acinetobacter baumannii is responsible for a growing number of the antibiotic-resistant infections in hospitals. Understanding the machinery of these bacteria used for initiation of pathogenesis, for recognition and activation of the immune system, and for development of antibiotic resistance are vital issues that require multi-disciplinary research strategies. The proposed work focuses on the development of advanced mass spectrometric approaches for characterization of the complex lipopolysaccharides (LPS), including the endotoxic lipid A sub-unit, that comprise the key constituents of the outer membrane of Gram-negative bacteria. Given the diversity seen in LPS and particularly lipid A structures, the structural characterizatio of LPS is a challenging task. We have begun to develop three photodissociation methods, including infrared multiphoton dissociation (IRMPD), ultraviolet photodissociation (UVPD), and activated-electron photodetachment dissociation (a-EPD), for the characterization of lipid A and LPS structures. Specific objectives include: 1) Photodissociation and hybrid MS/MS methods for characterization of lipid A and core oligosaccharide/O-antigens. The first aim entails systematic examination of the fragmentation patterns obtained by photodissociation and hybrid MS/MS methods for lipid A and oligosaccharide compounds. 2) Top-down characterization of LPS. Characterization of intact LPS will build by combining the fragmentation patterns obtained from bottom-up approaches (lipids and oligosaccharides) with information obtained from increasingly larger portions of the lipopolysaccharides via a middle-down strategy, then progressing to an integrated top-down workflow. 3) Development of an in silico database search algorithm. The complexity of the MS/MS spectra which contain an array of fragment ions from both the lipid and sugar portions makes their interpretation challenging. An in silico database search algorithm, MassMatrixLPS, will be developed by collaborator Hua Xu to facilitate automated, higher-throughput data analysis. 4) Applications to lipid A and LPS of H. pylori, C. jejuni, V. cholera, and E. coli. The collaboration forged between the Brodbelt and Trent groups is aimed at elucidating the LPS modification systems of three proteobacteria and elaborating their structure/function relationships. Specific biological problems include correlation of the structura changes of lipid A with the inflammatory response, unraveling the biosynthetic pathway of LPS, and elucidating the mechanism of resistance to antimicrobial peptides.
描述(申请人提供):革兰氏阴性细菌是世界上一些最致命和更广泛的流行病的罪魁祸首。幽门螺杆菌被认为是消化性溃疡和胃癌的主要原因,空肠弯曲杆菌和霍乱弧菌仍然是引起腹泻的最常见原因,鲍曼不动杆菌是医院越来越多的耐药感染的罪魁祸首。了解这些细菌用于启动发病机制、识别和激活免疫系统以及发展抗生素耐药性的机制是至关重要的,需要多学科的研究策略。拟议的工作重点是开发先进的质谱学方法来表征复杂的脂多糖(LPS),包括内毒素类脂A亚单位,它构成了革兰氏阴性细菌外膜的关键成分。鉴于脂多糖的多样性,特别是脂蛋白A的结构,脂多糖的结构特征是一项具有挑战性的任务。我们已经开发了三种光解离方法,包括红外多光子解离(IRMPD)、紫外光解离(UVPD)和激活电子光解离(a-EPD),用于表征脂蛋白A和脂多糖的结构。具体目标包括:1)光解离和混合MS/MS方法用于表征类脂A和核心低聚糖/O-抗原。第一个目标是系统地检查通过光解离和混合MS/MS方法获得的脂类A和寡糖化合物的裂解模式。2)自上而下的内毒素特征。通过将自下而上方法(脂类和低聚糖)获得的碎片模式与通过中间向下策略从越来越大的脂多糖部分获得的信息相结合,然后进行到自上而下的综合工作流程,将建立完整内毒素的特征。3)开发了一种在电子数据库中的搜索算法。MS/MS光谱的复杂性使得它们的解释具有挑战性,因为MS/MS光谱包含来自脂类和糖部分的一系列碎片离子。合作者徐华将开发一种电子数据库搜索算法MassMatrixLPS,以促进自动化、更高吞吐量的数据分析。4)幽门螺杆菌、空肠弯曲菌、霍乱弧菌、大肠杆菌对脂蛋白A和脂多糖的应用。Brodbelt和Trent小组之间的合作旨在阐明三种蛋白细菌的内毒素修饰系统,并阐述它们的结构/功能关系。具体的生物学问题包括脂类A的结构变化与炎症反应的相关性,解开内毒素的生物合成途径,阐明抗菌肽的耐药机制。

项目成果

期刊论文数量(0)
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Jennifer S. Brodbelt其他文献

Effects of functional group interactions on the bimolecular and dissociation reactions of diols
  • DOI:
    10.1016/1044-0305(92)85030-n
  • 发表时间:
    1992-07-01
  • 期刊:
  • 影响因子:
  • 作者:
    Erika S. Eichmann;Erwin Alvarez;Jennifer S. Brodbelt
  • 通讯作者:
    Jennifer S. Brodbelt
Evaluation of steric and substituent effects in phenols by competitive reactions of dimethyl ether ions in a quadrupole ion trap
  • DOI:
    10.1016/s1044-0305(05)80051-0
  • 发表时间:
    1995-08-01
  • 期刊:
  • 影响因子:
  • 作者:
    Gerald F. Bauerle;Jennifer S. Brodbelt
  • 通讯作者:
    Jennifer S. Brodbelt
Tracking molecular mobility
追踪分子迁移率
  • DOI:
    10.1038/nchem.382
  • 发表时间:
    2009-10-01
  • 期刊:
  • 影响因子:
    20.200
  • 作者:
    Jennifer S. Brodbelt
  • 通讯作者:
    Jennifer S. Brodbelt
Ultraviolet photoactivation perturbs the metal-ligand interface of atomically precise nanoclusters
紫外光活化干扰了原子精确纳米团簇的金属-配体界面
  • DOI:
    10.1039/d5cc00757g
  • 发表时间:
    2025-03-27
  • 期刊:
  • 影响因子:
    4.200
  • 作者:
    Anagha Jose;Jada N. Walker;Maya Khatun;Sami Malola;B. S. Sooraj;Hannu Häkkinen;Jennifer S. Brodbelt;Thalappil Pradeep
  • 通讯作者:
    Thalappil Pradeep
Correlation between Spectroscopic and Structural Features of Dimeric DNA-Templated Silver Nanoclusters using Mass Spectrometry
  • DOI:
    10.1016/j.bpj.2020.11.1731
  • 发表时间:
    2021-02-12
  • 期刊:
  • 影响因子:
  • 作者:
    Soonwoo Hong;Ines C. Santos;Yu-An Kuo;Yuan-I Chen;Trung D. Nguyen;Hsin-Chin Li;Pranav Anbarasu;Jennifer S. Brodbelt;Tim Yeh
  • 通讯作者:
    Tim Yeh

Jennifer S. Brodbelt的其他文献

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{{ truncateString('Jennifer S. Brodbelt', 18)}}的其他基金

Problem-to-Product Team Entrepreneurship and Active Mentoring (P2P-TEAM) Graduate Training Program
问题到产品团队创业与主动指导(P2P-TEAM)研究生培训计划
  • 批准号:
    10418608
  • 财政年份:
    2021
  • 资助金额:
    $ 27.87万
  • 项目类别:
Problem-to-Product Team Entrepreneurship and Active Mentoring (P2P-TEAM) Graduate Training Program
问题到产品团队创业与主动指导(P2P-TEAM)研究生培训计划
  • 批准号:
    10620850
  • 财政年份:
    2021
  • 资助金额:
    $ 27.87万
  • 项目类别:
Ultraviolet Photodissociation Mass Spectrometry for Characterization of Biological Molecules
用于表征生物分子的紫外光解离质谱法
  • 批准号:
    10320024
  • 财政年份:
    2021
  • 资助金额:
    $ 27.87万
  • 项目类别:
Ultraviolet Photodissociation Mass Spectrometry for Characterization of Biological Molecules
用于表征生物分子的紫外光解离质谱法
  • 批准号:
    10389836
  • 财政年份:
    2021
  • 资助金额:
    $ 27.87万
  • 项目类别:
Problem-to-Product Team Entrepreneurship and Active Mentoring (P2P-TEAM) Graduate Training Program
问题到产品团队创业与主动指导(P2P-TEAM)研究生培训计划
  • 批准号:
    10089703
  • 财政年份:
    2021
  • 资助金额:
    $ 27.87万
  • 项目类别:
Ultraviolet Photodissociation Mass Spectrometry for Characterization of Biological Molecules
用于表征生物分子的紫外光解离质谱法
  • 批准号:
    10797256
  • 财政年份:
    2021
  • 资助金额:
    $ 27.87万
  • 项目类别:
Ultraviolet Photodissociation Mass Spectrometry for Characterization of Biological Molecules
用于表征生物分子的紫外光解离质谱法
  • 批准号:
    10543449
  • 财政年份:
    2021
  • 资助金额:
    $ 27.87万
  • 项目类别:
Interpretation of the phosphorylation code of RNA polymerase II during eukaryotic transcription
真核转录过程中RNA聚合酶II磷酸化密码的解读
  • 批准号:
    9751900
  • 财政年份:
    2018
  • 资助金额:
    $ 27.87万
  • 项目类别:
Interpretation of the phosphorylation code of RNA polymerase II during eukaryotic transcription
真核转录过程中RNA聚合酶II磷酸化密码的解读
  • 批准号:
    10158496
  • 财政年份:
    2018
  • 资助金额:
    $ 27.87万
  • 项目类别:
UVPD Mass Spectrometry of Protein Complexes
蛋白质复合物的 UVPD 质谱分析
  • 批准号:
    9217240
  • 财政年份:
    2017
  • 资助金额:
    $ 27.87万
  • 项目类别:

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