LIPOOLIGOSACCHARIDE BIOSYNTHESIS IN NEISSERIACEAE

淋病奈瑟菌感染L百余万例 以及每年与淋病相关的总医疗费用 治疗淋病和感染引起的并发症 由这种生物每年超过L十亿美元。一个密切相关的 病原体脑膜炎奈瑟氏菌可导致严重的发病率和死亡率。 全世界。如果预防这些疾病的有效疫苗 如果有了，医疗保健成本将大大降低。这个 淋球菌具有各种各样的表面结构，可以 作为致病的毒力决定因素。脂低聚糖(LOS)是 最不为人所知的细胞表面抗原，包括化学和 从基因上讲，即使这些分子介导了大部分毒性损害 在输卵管中，负责激活细胞上的补体 表面，并作为杀菌抗体的靶标。此外， 针对脂多糖的抗体对多种病毒具有保护作用 革兰氏阴性感染。一种能刺激反洛杉矶运动的疫苗 这种反应可能对淋球菌和脑膜炎双球菌都有保护作用。 感染。由于淋球菌和脑膜炎双球菌LO共享许多表位， 以及所有与LOS相关的已被识别的基因 生物合成在两个物种中都是保守的，收集到的关于LOS的信息 一个物种的生物合成将直接适用于另一个物种。 这项提案将重点放在淋球菌中的LOS生物合成上。会的 通过基因克隆和遗传互补技术鉴定基因 LOS生物合成所必需的，通过DNA序列来表征基因 分析、定义基因产物的生化特性和 确定淋球菌调节其生长的机制 综合。如果洛杉矶要被用作候选疫苗，我们需要 拥有能稳定产生所需表位的淋球菌菌株。 因为淋球菌可以根据宿主和局部的不同而改变其LO 环境中，对其合成的遗传调控的研究进展 这是正当的。如果我们需要定义良好、稳定的LOS产生菌株 是为了剖析LOS在疾病过程中的作用。通过理解 淋球菌是如何产生LOS的，就有可能构建菌株 具有定义的LOS。这些菌株将成为未来研究的基础 LOS在疾病过程中的作用。

Neisseria gonorrhoeae is responsible for over l million cases of gonorrhea each year, and the total health care costs associated with treating gonorrhea and complications that arise from infections caused by this organism exceed l billion dollars per year. A closely related pathogen, N. meningitidis, causes significant morbidity and mortality worldwide. If effective vaccines to prevent these diseases were available, health care costs would be dramatically reduced. The gonococcus possesses a wide variety of surface structures that can serve as virulence determinants for pathogenesis. Lipooligosaccharide (LOS) is the least understood cell surface antigen, both chemically and genetically, even though these molecules mediate most of the toxic damage in fallopian tubes, are responsible for complement activation on the cell surface, and serve as the target for bactericidal antibody. Furthermore, antibody directed against lipopolysaccharide is protective for a variety of Gram-negative infections. A vaccine that stimulated an anti-LOS response might be protective for both gonococcal and meningococcal infections. Since gonococcal and meningococcal LOS share many epitopes, and all of the genes that have been identified that are involved in LOS biosynthesis are conserved in both species, information gleaned about LOS biosynthesis in one species will be directly applicable to the other. This proposal will focus on LOS biosynthesis in the gonococcus. It will identify by gene cloning and genetic complementation techniques, genes required for LOS biosynthesis, characterize the genes by DNA sequence analysis, define the biochemical properties of the gene products and determine the mechanisms by which the gonococcus regulates their synthesis. If LOS is to be exploited as a vaccine candidate, we need to have strains of the gonococcus that stably produce the desired epitopes. Since the gonococcus can vary its LOS, depending on the host, and local environment, studies on the genetic regulation of its synthesis are warranted. Well defined, stable LOS producing strains are needed if we are to dissect the role of LOS in the disease process. By understanding how the gonococcus makes LOS, it will be possible to construct strains with defined LOS. These strains will be the basis of future studies into the role of LOS in the disease process.