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LIPOOLIGOSACCHARIDE BIOSYNTHESIS IN NEISSERIACEAE

奈瑟菌科中脂寡糖的生物合成

基本信息

批准号：
6740890
负责人：
DANIEL C STEIN
金额：
$ 25.9万
依托单位：
UNIV OF MARYLAND, COLLEGE PARK
依托单位国家：
美国
项目类别：
财政年份：
1988
资助国家：
美国
起止时间：
1988-09-30 至 2006-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6740890
关键词：
Escherichia coli Neisseria gonorrhoeae bacterial antigens bacterial genetics carbohydrate biosynthesis endotoxins enzyme activity gene complementation gene expression genetic polymorphism genetic strain glycosyltransferase lipopolysaccharides molecular cloning mutant nucleic acid sequence oligosaccharides

项目摘要

Description (adapted from the applicant's abstract): Neisseria gonorrhoeae is responsible for over 1 million cases of gonorrhea each year in the United States and the total health care costs associated with treating gonorrhea, and complications that arise from infections caused by this organism exceed 1 billion dollars per year. An effective vaccine would dramatically reduce the associated health care costs. This proposal focuses on elucidating the genetic mechanisms responsible for the expression of one of the organism's principal surface antigens, lipooligosaccharide (LOS). In the work to be described, I will identify by gene cloning and genetic complementation techniques, genes required for the LOS biosynthesis. I will characterize these genes by DNA sequence analysis, define the biochemical properties of the gene products and determine their role in the biosynthetic process. Since the gonococcus can vary its LOS, depending on the host and the local environment, studies on the genetic regulation of its synthesis are warranted. Stable LOS-producing strains are needed to allow us to dissect the role of LOS in the disease process. I will construct a series of genetically defined LOS mutants that express defined LOS structures. These strains will also allow us to study the interaction of the expression of this molecule with other cell surface components. Understanding how the expression of LOS is regulated will allow us to design experiments to test the role of each cell surface component in the disease process. By understanding the relationship between disease and the expression of a specific surface component, we can design vaccines that can prevent the disease in specific demographic groups.

描述（改编自申请人的摘要）：淋病奈瑟菌是美国每年造成超过 100 万例淋病病例各州以及与治疗淋病相关的总医疗保健费用，以及由该微生物引起的感染引起的并发症超过 1 每年十亿美元。有效的疫苗将大大减少相关的医疗保健费用。该提案的重点是阐明遗传负责表达生物体主要功能之一的机制表面抗原，脂寡糖（LOS）。在即将描述的工作中，我将通过基因克隆和基因互补技术鉴定基因 LOS 生物合成所需的。我将通过 DNA 来表征这些基因序列分析，定义基因产物的生化特性和确定它们在生物合成过程中的作用。由于淋球菌可能有所不同其LOS，取决于主机和本地环境，研究其合成的遗传调控是有保证的。稳定的 LOS 产生菌株我们需要这些信息来剖析 LOS 在疾病过程中的作用。我将构建一系列基因定义的 LOS 突变体，表达定义的 LOS 结构。这些菌株还将使我们能够研究相互作用该分子与其他细胞表面成分的表达。了解 LOS 的表达是如何调节的将使我们能够设计测试每种细胞表面成分在疾病中的作用的实验过程。通过了解疾病与表达之间的关系利用特定的表面成分，我们可以设计疫苗来预防特定人口群体的疾病。