LIPOOLIGOSACCHARIDE BIOSYNTHESIS IN NEISSERIACEAE

淋病奈瑟菌和脑膜炎奈瑟菌是人类重要的病原体。那里 淋病的病例比脑膜炎球菌性脑膜炎多得多，但是 脑膜炎是一种更严重的疾病，原因是与 死亡率。一种有效的疫苗将防止发病率和 这些疾病造成的死亡率和相关的医疗保健减少 成本。由于各种原因，疫苗的开发一直受到阻碍。 目前尚不清楚个别成分在这种疾病中起什么作用 过程，也不是什么成分引起交叉反应的保护性免疫 回应。关于这些生物的毒力决定因素的研究是 进一步阻碍了这些病原体通过抗原性 以及它们的表面抗原的相变。抗原性变异有 过去从许多研究中获得的混淆数据是因为细胞 被研究的生物体的表面可能在 这项研究。脂寡糖(LOS)在发病机制中的重要性 这些生物的免疫生物学是毋庸置疑的。失去是一家人 具有许多抗原决定簇的复杂大分子 在自然免疫和获得性免疫中很重要。淋病奈瑟氏菌LOS和 脑膜炎奈瑟菌在组成和一级结构上都是相似的。 它们与几种非致病性病毒具有共同的抗原性 Neisseria sp.LOS在大小上的变化，由移动性测量 十二烷基硫酸钠-PAGE凝胶，是由于糖基数目的不同，2- 酮-3-脱氧辛酸酯(KDO)和/或己糖胺。抗原性差异 菌株之间的差异也可以由各种糖类的取代引起 连接糖的连接键的单位或改变。一个 了解LOS生物合成的遗传学是很重要的，如果我们 确定刺激疾病症状和/或 产生保护性免疫反应。了解猪瘟的免疫生物学 LOS可能导致疫苗的开发，其方式类似于 已经在其他生物身上完成了。要检验的总体假设 是：“我们能构建具有特定LOS结构的菌株吗？”，“我们能吗？” 使用具有定义的LOS结构的菌株来确定这些 在疾病过程中起作用的成分？“；以及”可以使用这些菌株吗？“ 在人类身上诱导保护性免疫反应？“这些假说 将使用分子遗传学方法进行测试。

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.