LIPOOLIGOSACCHARIDE BIOSYNTHESIS IN NEISSERIACEAE

简介(摘自申请者摘要)：淋病奈瑟菌 每年在美国造成100多万例淋病 各州和与治疗淋病相关的总医疗费用，以及 由该细菌引起的感染引起的并发症超过1 每年十亿美元。一种有效的疫苗将大大减少 相关的医疗保健费用。这项建议的重点是阐明基因 生物体的一种主要基因表达的机制 表面抗原，脂低聚糖(LOS)。在将要描述的工作中，我 将通过基因克隆和遗传互补技术识别基因 是LOS生物合成所必需的。我将用DNA来描述这些基因 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。因为淋球菌可能会发生变化 它的损失，取决于宿主和当地环境，研究 对其合成的遗传调控是有根据的。稳定产LOS菌株 使我们能够剖析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 该分子与其他细胞表面成分的表达。 了解LOS的表达是如何被调控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 进程。通过理解疾病和表情之间的关系 对于特定的表面成分，我们可以设计疫苗来预防 疾病在特定的人口群体中。

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.