Biosynthesis & Function of a Bacillus anthracis-specific cell wall polysaccharide

生物合成

基本信息

  • 批准号:
    7860446
  • 负责人:
  • 金额:
    $ 18.56万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2009
  • 资助国家:
    美国
  • 起止时间:
    2009-06-05 至 2012-05-30
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): Our laboratory has recently reported the structure of a Bacillus anthracis species-specific polysaccharide. This polysaccharide (termed HF-PS) has been classified a 'non-classical' secondary cell wall polymer. It is isolated from the cell wall of vegetative cells by treatment with aqueous hydrogen fluoride (HF), and was previously reported to function in anchoring/exporting the S-layer proteins, Sap and EA1, to the cell surface. Our work strongly supports that the HF-PS is structurally specific to B. anthracis strains, is immunogenic in that animals injected with live or dead spores of B. anthracis Sterne (34F2) produce antibodies against HF-PS, and is immunogenically specific with regard to the binding of these antibodies to the HF-PSs of even closely related B. cereus strains. Further, we have shown that sera from Rhesus macaques that survive exposure to B. anthracis spores contain IgG anti-HF-PS antibodies. Preliminary data and results in the literature support that these polysaccharides could be crucial for important functions with regard to the growth and virulence of pathogenic Bacillus species, including B. anthracis. However, to date direct empirical evidence is still missing. The aims of this proposal are to engineer mutants that are impaired in the biosynthesis of this HF-PS polysaccharide and to characterize the phenotype of these mutants with regard to their growth, sporulation, HF-PS structure, HF-PS interaction with S-layer proteins and various phage endolysins, and to study the effect of each mutation on the virulence in a mouse model. This research will provide us with necessary insight regarding the HF-PS's pathogenic functions, and its usefulness for the development of vaccines, diagnostics and therapeutics. PUBLIC HEALTH RELEVANCE: The bacterium Bacillus anthracis causes anthrax in humans; as a bioterrorism agent the bacteria are a threat to public health. Our laboratory has recently reported a cell wall polysaccharide of a B. anthracis (termed HF- PS) with a structure specific to these bacteria. We will create B. anthracis mutants impaired in the biosynthesis of this cell wall polysaccharide and investigate whether these mutants are impaired in important bacterial growth functions and disease development. This investigation will lay the groundwork for future studies into improved vaccines, diagnostics, and therapeutics, and into new anthrax-related public health practices.
描述(由申请人提供):我们的实验室最近报道了炭疽芽孢杆菌物种特异性多糖的结构。这种多糖(称为 HF-PS)已被归类为“非经典”次生细胞壁聚合物。它是通过氟化氢 (HF) 水溶液处理从营养细胞的细胞壁中分离出来的,之前有报道称它具有将 S 层蛋白 Sap 和 EA1 锚定/输出到细胞表面的功能。我们的工作强烈支持HF-PS在结构上对炭疽芽孢杆菌菌株具有特异性,具有免疫原性,因为注射炭疽芽孢杆菌Sterne(34F2)活或死孢子的动物会产生针对HF-PS的抗体,并且对于这些抗体与甚至密切相关的蜡样芽孢杆菌菌株的HF-PS的结合也具有免疫原性特异性。此外,我们还发现,暴露于炭疽芽孢杆菌孢子后仍存活的恒河猴血清中含有 IgG 抗 HF-PS 抗体。文献中的初步数据和结果表明,这些多糖对于致病性芽孢杆菌(包括炭疽芽孢杆菌)的生长和毒力的重要功能至关重要。然而,迄今为止,仍然缺乏直接的经验证据。该提案的目的是设计这种 HF-PS 多糖生物合成受损的突变体,并表征这些突变体的表型,包括其生长、孢子形成、HF-PS 结构、HF-PS 与 S 层蛋白和各种噬菌体内溶素的相互作用,并研究每种突变对小鼠模型毒力的影响。这项研究将为我们提供有关 HF-PS 致病功能及其对开发疫苗、诊断和治疗的有用性的必要见解。公共卫生相关性:炭疽杆菌会引起人类炭疽病;作为一种生物恐怖主义媒介,细菌对公众健康构成威胁。我们的实验室最近报道了炭疽芽孢杆菌的细胞壁多糖(称为 HF-PS),其具有这些细菌特有的结构。我们将创建这种细胞壁多糖生物合成受损的炭疽芽孢杆菌突变体,并研究这些突变体的重要细​​菌生长功能和疾病发展是否受损。这项调查将为未来改进疫苗、诊断和治疗方法以及与炭疽相关的新公共卫生实践的研究奠定基础。

项目成果

期刊论文数量(6)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Structural and immunochemical relatedness suggests a conserved pathogenicity motif for secondary cell wall polysaccharides in Bacillus anthracis and infection-associated Bacillus cereus.
结构和免疫化学相关性表明,炭疽芽孢杆菌和感染相关的蜡状芽孢杆菌中二级细胞壁多糖的保守致病基序。
  • DOI:
    10.1371/journal.pone.0183115
  • 发表时间:
    2017
  • 期刊:
  • 影响因子:
    3.7
  • 作者:
    Kamal N;Ganguly J;Saile E;Klee SR;Hoffmaster A;Carlson RW;Forsberg LS;Kannenberg EL;Quinn CP
  • 通讯作者:
    Quinn CP
Ribosylhopane, a novel bacterial hopanoid, as precursor of C35 bacteriohopanepolyols in Streptomyces coelicolor A3(2).
  • DOI:
    10.1002/cbic.201402261
  • 发表时间:
    2014-09-22
  • 期刊:
  • 影响因子:
    3.2
  • 作者:
    Liu, Wenjun;Sakr, Elias;Schaeffer, Philippe;Talbot, Helen M.;Donisi, Janina;Haertner, Thomas;Kannenberg, Elmar;Takano, Eriko;Rohmer, Michel
  • 通讯作者:
    Rohmer, Michel
Lipopolysaccharide O-chain core region required for cellular cohesion and compaction of in vitro and root biofilms developed by Rhizobium leguminosarum.
豆根瘤菌形成的体外和根生物膜的细胞凝聚和压实所需的脂多糖 O 链核心区域。
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RUSSELL W CARLSON其他文献

RUSSELL W CARLSON的其他文献

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{{ truncateString('RUSSELL W CARLSON', 18)}}的其他基金

Rhizobial Lipopolysaccharides Essential for Infection
感染必需的根瘤菌脂多糖
  • 批准号:
    8008946
  • 财政年份:
    2010
  • 资助金额:
    $ 18.56万
  • 项目类别:
Biosynthesis & Function of a Bacillus anthracis-specific cell wall polysaccharide
生物合成
  • 批准号:
    7739417
  • 财政年份:
    2009
  • 资助金额:
    $ 18.56万
  • 项目类别:
Bacillus anthracis cell surface carbohydrates
炭疽芽孢杆菌细胞表面碳水化合物
  • 批准号:
    6803538
  • 财政年份:
    2003
  • 资助金额:
    $ 18.56万
  • 项目类别:
Bacillus anthracis cell surface carbohydrates
炭疽芽孢杆菌细胞表面碳水化合物
  • 批准号:
    6673663
  • 财政年份:
    2003
  • 资助金额:
    $ 18.56万
  • 项目类别:
STRUCTURAL DETERMINATION OF THE LPS FROM RHIZOBIUM
根瘤菌 LPS 的结构测定
  • 批准号:
    2179936
  • 财政年份:
    1988
  • 资助金额:
    $ 18.56万
  • 项目类别:
STRUCTURAL DETERMINATION OF THE LPS FROM RHIZOBIUM
根瘤菌 LPS 的结构测定
  • 批准号:
    2179937
  • 财政年份:
    1988
  • 资助金额:
    $ 18.56万
  • 项目类别:
STRUCTURAL DETERMINATION OF THE LPS FROM RHIZOBIUM
根瘤菌 LPS 的结构测定
  • 批准号:
    3296709
  • 财政年份:
    1988
  • 资助金额:
    $ 18.56万
  • 项目类别:
Rhizobial Lipopolysaccharides Essential for Infection
感染必需的根瘤菌脂多糖
  • 批准号:
    6624026
  • 财政年份:
    1988
  • 资助金额:
    $ 18.56万
  • 项目类别:
STRUCTURAL DETERMINATION OF THE LPS FROM RHIZOBIUM
根瘤菌 LPS 的结构测定
  • 批准号:
    2179935
  • 财政年份:
    1988
  • 资助金额:
    $ 18.56万
  • 项目类别:
STRUCTURAL DETERMINATION OF THE LPS FROM RHIZOBIUM
根瘤菌 LPS 的结构测定
  • 批准号:
    3296705
  • 财政年份:
    1988
  • 资助金额:
    $ 18.56万
  • 项目类别:

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