Bacillus anthracis cell surface carbohydrates

炭疽芽孢杆菌细胞表面碳水化合物

• 批准号: 6803538
• 负责人: RUSSELL W CARLSON
• 金额: $ 29.44万
• 依托单位: UNIVERSITY OF GEORGIA
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-30 至 2006-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6803538
• 关键词: Bacillus anthracis; antibacterial agents; bacterial proteins; bacterial vaccines; biotechnology; bioterrorism /chemical warfare; carbohydrate structure; cell membrane; cell wall; cooperative study; diagnosis design /evaluation; drug design /synthesis /production; gel filtration chromatography; gene expression; genetic strain; high performance liquid chromatography; ion exchange chromatography; liquid chromatography mass spectrometry; mass spectrometry; matrix assisted laser desorption ionization; nuclear magnetic resonance spectroscopy; polysaccharides; protein binding; vaccine development; virulence

DESCRIPTION (provided by applicant): The bioterrorist threat with regard to Bacillus anthracis requires the development of improved vaccines, diagnostic, and therapeutic agents. Bacterial cell surface carbohydrates have been utilized for all three of these purposes, however, little is known about the B. anthracis cell wall carbohydrates. B. anthracis produces a capsule consisting of poly-g-glutamic acid, rather than a polysaccharide. However, recent work has shown that there are important carbohydrate components in both the vegetative and spore forms of B.anthracis. The vegetative cell wall contains a polysaccharide that is linked to peptidoglycan and serves to anchor the crystalline surface (S-layer) protein to the cell wall by binding with the SLH domain of the protein. This polysaccharide is referred to as the S-layer anchoring polysaccharide. The exosporium coat of the spore contains a major glycoprotein that is an immunodominant antigen of the spore. While the structure of the S-layer anchoring polysaccharide has not been determined, indirect data suggest that it has structural features that are specific to B. anthracis. There are no reports characterizing the carbohydrates of the exosporium glycoprotein. It is hypothesized that the B. anthracis cell wall contains carbohydrates (e.g. the S-layer anchoring polysaccharide and the exosporium glycoprotein) that are species and/or strain specific and are, therefore, candidates for the development of vaccines, diagnostic and therapeutic agents. The specific aims of this application are to (a.) determine if the S-layer anchoring polysaccharide and the exosporium carbohydrates have species specific structural features, (b.) determine if these same carbohydrates have strain specific structural features, and (c.) determine if the B. anthracis virulence plasmids, pX01 and pX02, encode for enzymes that structurally modify these carbohydrates. This work will be done by isolating and structurally characterizing these carbohydrates from several species of the B. cereus group, including B. anthracis var Ames, from several strains/isolates of B. anthracis, and from B.anthracis var Ames derivatives that have been differentially cured of pX01 or pX02, or of both plasmids. This work will be a collaborative effort between Dr. Russell Carlson at the Complex Carbohydrate Research Center at the University of Georgia, Dr. David Stephens at Emory University, and Dr. Conrad Quinn at the Centers for Disease Control.

描述（由申请人提供）：关于炭疽芽孢杆菌的生物恐怖主义威胁需要开发改进的疫苗，诊断和治疗剂。 细菌细胞表面碳水化合物已用于所有这三个目的，但是，对炭疽芽孢杆菌细胞壁碳水化合物知之甚少。 B.炭疽病产生由聚-G-谷氨酸而不是多糖组成的胶囊。 然而，最近的工作表明，在植物的营养和孢子形式中都有重要的碳水化合物成分。 营养细胞壁含有与肽聚糖有关的多糖，并通过与蛋白质的SLH结构域结合，将晶体表面（S-层）蛋白锚定在细胞壁上。 该多糖称为S层锚定多糖。 孢子的外孢子层含有一种主要的糖蛋白，是孢子的免疫主导抗原。 尽管尚未确定S层锚定多糖的结构，但间接数据表明它具有特定于炭疽芽孢杆菌的结构特征。 没有表征外孢菌素糖蛋白的碳水化合物的报道。 假设炭疽芽孢杆菌细胞壁含有碳水化合物（例如S层锚定多糖和/或特异性菌株），因此是诊断和治疗剂的疫苗开发的候选者。 该应用的具体目的是（a。）确定锚定多糖和碳孢子的S层具有物种特定的结构特征，（b。）确定这些相同的碳水化合物是否具有特定的特定结构特征，（c。）确定蒽固醇含量px01和PX01和PX02，构造这些代码的邻苯二甲酸芽孢杆菌是否确定这些含量。 这项工作将是通过从脑芽孢杆菌组的几种碳水化合物组中隔离和结构表征这些碳水化合物的来完成的，这些碳水化合物（包括炭疽芽孢杆菌。 这项工作将是佐治亚大学复杂碳水化合物研究中心的Russell Carlson博士，埃默里大学的David Stephens博士与疾病控制中心的Conrad Quinn博士之间的合作努力。