LIPOOLIGOSACCHARIDE BIOSYNTHESIS IN NEISSERIACEAE

奈瑟菌科中脂寡糖的生物合成

• 批准号: 2376248
• 负责人: DANIEL C STEIN
• 金额: $ 6.59万
• 依托单位: UNIV OF MARYLAND, COLLEGE PARK
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-08-01 至 2000-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2376248
• 关键词: Neisseria gonorrhoeae; Neisseria meningitidis; bacterial antigens; bacterial meningitis; carbohydrate structure; gel mobility shift assay; gene expression; gene targeting; glycolipids; gonorrhea; lipid biosynthesis; lipopolysaccharides; molecular cloning; western blottings

N. Gonorrhoeae and N. Meningitidis are important human pathogens. There are many more cases of gonorrhea then meningococcal meningitis, but meningitis is a much more serious disease due to the associated mortality. An effective vaccine would prevent the morbidity and mortality caused by these diseases and reduce the associated health care costs. Vaccine development has been hampered for a variety of reasons. It is not clear what role individual components play in the disease process, nor what components elicit a cross-reactive protective immune response. Studies on virulence determinants in these organisms are further hampered by the fact that these pathogens undergo both antigenic and phase variation of their surface antigens. Antigenic variation has obfuscated data obtained from many studies in the past because the cell surface of the organisms under study may have changed over the course of the study. The importance of lipooligosaccharide (LOS) in the pathogenesis and immunobiology of these organisms is unquestioned. LOSs are a family of complex macromolecules possessing many antigenic determinants that are important in natural and acquired immunity. LOS from N. Gonorrhoeae and N. Meningitidis are similar, both in composition and primary structure. They share antigenic properties with several of the nonpathogenic Neisseria sp. The variation of LOS in size, as measured by mobility on SDS-PAGE gels, is due to differences in the number of glycose units, 2- keto-3-deoxyoctonates (KDO), and/or hexosmines. Antigenic differences between strains can also result from substitutions of various glycose units or alterations of the linkages that connect the sugars. An understanding of the genetics of LOS biosynthesis is important if we are to define the conformations that stimulate disease symptoms and/or generate protective immune responses. Understanding the immunobiology of LOS may lead to the development of vaccines in a manner similar to what has been done with other organisms. The overall hypotheses to be tested are: "Can one construct strains with defined LOS structures?", "Can one use strains with defined LOS structures to determine the role that these components play in the disease process?"; and "Can one use these strains to induce a protective immune response - in humans?" These hypotheses will be tested using a molecular genetic approach.

N.淋病奈瑟菌（N.脑膜炎是重要的人类病原体。 那里 淋病的病例比脑膜炎球菌性脑膜炎多得多， 脑膜炎是一种更为严重的疾病， mortality. 一种有效的疫苗可以防止发病， 这些疾病造成的死亡率，并减少相关的医疗保健 成本 疫苗开发因各种原因而受阻。 目前尚不清楚个别成分在疾病中起什么作用 过程，也不是什么成分引起交叉反应性保护性免疫 反应 对这些生物的毒力决定因子的研究是 进一步受到这些病原体经历抗原性 和其表面抗原的相位变化。 抗原变异具有 混淆了过去许多研究中获得的数据，因为细胞 研究中的生物体表面可能在整个过程中发生了变化。 书房脂寡糖（LOS）在发病机制中的重要性 这些生物体的免疫生物学是毋庸置疑的。 迷失是一个家庭 具有许多抗原决定簇的复杂大分子， 在自然和获得性免疫中很重要。 从N。淋病和 N.脑膜炎在组成和初级结构上都是相似的。 它们与几种非致病性的 奈瑟氏菌属。LOS大小的变化，通过在 SDS-PAGE凝胶，是由于在糖单位，2- 酮-3-脱氧辛酸酯（KDO）和/或己糖胺。 抗原差异 菌株之间的差异也可能是由于各种葡萄糖的取代 连接糖的键的单元或改变。 一个 了解LOS生物合成的遗传学是重要的，如果我们 定义刺激疾病症状的构象和/或 产生保护性免疫反应。 了解免疫生物学 LOS可能会导致疫苗的发展，其方式类似于 已经在其他生物身上做过了。 待检验的总体假设 问题是：“可以用定义的LOS结构构建菌株吗？”、“能不能一个 使用具有定义的服务水平结构的应变来确定这些应变的作用， 在疾病过程中起作用的成分？“;和“可以使用这些菌株吗 来诱导保护性免疫反应“这些假设 将使用分子遗传学方法进行测试。