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

生物合成

• 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
• 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

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“非经典的”次生细胞壁聚合物。它是通过用氟化氢水溶液（HF）处理从营养细胞的细胞壁中分离出来的，并且先前报道其在将S层蛋白Sap和EA 1锚定/输出到细胞表面中起作用。我们的工作有力地支持了HF-PS在结构上对B具有特异性。炭疽菌菌株，是免疫原性的，因为动物注射了B的活孢子或死孢子。炭疽菌Sterne（34 F2）产生抗HF-PS的抗体，并且对于这些抗体与甚至密切相关的B的HF-PS的结合是免疫原性特异性的。蜡状芽孢杆菌菌株。此外，我们已经表明，恒河猴的血清暴露于B。炭疽孢子含有IgG抗HF-PS抗体。文献中的初步数据和结果支持这些多糖对于致病性芽孢杆菌属物种（包括B）的生长和毒力的重要功能可能是至关重要的。炭疽病然而，迄今为止，直接的经验证据仍然缺失。该提案的目的是工程突变体，在这种HF-PS多糖的生物合成受损，并表征这些突变体的表型，关于它们的生长，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，并研究每个突变对小鼠模型中的毒力的影响。这项研究将为我们提供必要的了解HF-PS的致病功能，以及其对疫苗，诊断和治疗的发展。公共卫生关系：炭疽杆菌在人类中引起炭疽病;作为一种生物恐怖主义制剂，这种细菌对公众健康构成威胁。我们实验室最近报道了一种B的细胞壁多糖。炭疽菌（称为HF-PS）具有这些细菌特有的结构。我们将创建B。炭疽菌突变体在这种细胞壁多糖的生物合成中受损，并研究这些突变体是否在重要的细菌生长功能和疾病发展中受损。这项调查将为今后研究改进疫苗、诊断和治疗方法以及新的炭疽相关公共卫生实践奠定基础。

项目成果

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: 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

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。

• DOI: 10.1128/aem.03175-14
• 发表时间: 2015
• 期刊: Applied and environmental microbiology
• 影响因子: 4.4
• 作者: Russo DM

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