Bacillus anthracis cell surface carbohydrates

炭疽芽孢杆菌细胞表面碳水化合物

基本信息

批准号：
6673663
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
项目类别：
财政年份：
2003
资助国家：
美国
起止时间：
2003-09-30 至 2005-09-29
项目状态：
已结题

项目摘要

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）：炭疽杆菌的生物恐怖威胁需要开发改进的疫苗、诊断剂和治疗剂。细菌细胞表面碳水化合物已被用于所有这三个目的，然而，人们对炭疽芽孢杆菌细胞壁碳水化合物知之甚少。炭疽芽孢杆菌产生一种由聚-g-谷氨酸而不是多糖组成的胶囊。然而，最近的研究表明，炭疽芽孢杆菌的营养体和孢子形式中都含有重要的碳水化合物成分。营养细胞壁含有与肽聚糖连接的多糖，通过与蛋白质的 SLH 结构域结合，将晶体表面（S 层）蛋白质锚定到细胞壁上。这种多糖被称为S层锚定多糖。孢子的外孢壁含有主要糖蛋白，它是孢子的免疫显性抗原。虽然 S 层锚定多糖的结构尚未确定，但间接数据表明它具有炭疽芽孢杆菌特有的结构特征。没有报道描述孢子外糖蛋白的碳水化合物。据推测，炭疽芽孢杆菌细胞壁含有物种和/或菌株特异性的碳水化合物（例如S层锚定多糖和孢子外糖蛋白），因此是开发疫苗、诊断和治疗剂的候选者。本申请的具体目的是 (a.) 确定 S 层锚定多糖和孢子外碳水化合物是否具有物种特异性结构特征，(b.) 确定这些相同的碳水化合物是否具有菌株特异性结构特征，以及 (c.)确定炭疽芽孢杆菌毒力质粒 pX01 和 pX02 是否编码对这些碳水化合物进行结构修饰的酶。这项工作将通过从蜡样芽孢杆菌组的几个物种中分离和结构表征这些碳水化合物来完成，包括炭疽芽孢杆菌艾姆斯变种、炭疽芽孢杆菌的几种菌株/分离物以及已被鉴定的炭疽芽孢杆菌变种衍生物。 pX01 或 pX02 或两种质粒的差异修复。这项工作将由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 博士和疾病控制中心的 Conrad Quinn 博士合作完成。