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：
RUSSELL W CARLSON
金额：
$ 18.56万
依托单位：
UNIVERSITY OF GEORGIA
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

来源：
https://reporter.nih.gov/project-details/7860446
关键词：
Address Affect Anabolism Animals Anthrax disease Antibodies Antigens Autolysin Bacillus (bacterium)Bacillus anthracis Bacillus anthracis spore Bacillus cereus Bacteria Bacteriophages Binding Binding Proteins Bioterrorism Carbohydrates Cell Surface Proteins Cell Wall Cell surface Cells Data Deletion Mutation Development Diagnostic Disease Engineering Enzymes Evaluation Exposure to Funding Future Gene Expression Genes Genome Growth Growth and Development function Human Hydrogen Fluoride Immune Sera Institutes Investigation Knowledge Laboratories Letters Life Literature Macaca mulatta Measures Medical Research Mutagenesis Mutation Parents Pathogenicity Pathway interactions Peptidoglycan Phenotype Physiological Plasmids Polymers Polysaccharides Preparation Primates Property Prophages Proteins Public Health Public Health Practice Publications Regulation Reporting Research Role Serum Staging Structure Temperature Therapeutic Transferase Transferase Gene UDP-N-acetylglucosamine 2-epimerase Vaccinated Vaccines Virulence Virulence Factors Work anti-IgG aqueous base cell envelope cell growth endolysin falls gene synthesis immunogenic improved insight lysin mouse model mutant novel public health relevance vaccine development

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告了炭疽芽孢杆菌特异性多糖的结构。该多糖（称为HF-PS）已被分类为“非经典”次级细胞壁聚合物。它通过用氟化水（HF）处理从营养细胞的细胞壁中分离出来，并以前据报道在将S-layer蛋白，SAP和EA1锚定/导出到细胞表面中起作用。我们的工作强烈支持HF-PS在结构上是针对炭疽芽孢杆菌菌株的特异性的，具有免疫原性，因为那些注射了嗜血芽孢杆菌的活孢子或死孢子的动物（34F2）可产生针对HF-PS的抗体，并且在这些抗体与HF-PES的结合方面是免疫剂的特定于HF-PESS均与HF-PESSS的结合。此外，我们已经表明，来自恒河猕猴的猕猴的血清含有炭疽芽孢杆菌孢子，其中含有IgG抗HF-PS抗体。初步数据并导致文献支持这些多糖对于重要功能至关重要，这对于包括炭疽芽孢杆菌在内的致病性芽孢杆菌的生长和毒力至关重要。但是，迄今为止直接经验证据仍然缺失。该提议的目的是在这种HF-PS多糖的生物合成中受到影响的工程突变体，以表征这些突变体在其生长，孢子形成，HF-PS结构方面的表型，HF-PS与S层蛋白质和各种Phage Endolysins的相互作用，以研究每种变形的效果。这项研究将为我们提供有关HF-PS的致病功能及其对疫苗，诊断和治疗剂开发的有用性的必要见解。公共卫生相关性：炭疽菌细菌在人类中引起炭疽病；作为生物恐怖剂，细菌是对公共卫生的威胁。我们的实验室最近报道了炭疽芽孢杆菌（称为HF-PS）的细胞壁多糖，其结构是这些细菌的特异性结构。我们将在该细胞壁多糖的生物合成中创建炭疽芽孢杆菌突变体受损，并研究这些突变体在重要的细菌生长功能和疾病发育中是否受到损害。这项调查将为未来的研究奠定基础，以改善疫苗，诊断和治疗疗法，并将其纳入与炭疽病相关的新公共卫生实践中。

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.

DOI：
10.1371/journal.pone.0183115
发表时间：
2017
期刊：
PloS one
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：
CHEMBIOCHEM
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。