Genetic Variation in genes involved in Neisseria gonorrhoeae LOS biosynthesis

淋病奈瑟菌 LOS 生物合成相关基因的遗传变异

• 批准号: 8415937
• 负责人: DANIEL C STEIN
• 金额: $ 20.73万
• 依托单位: UNIV OF MARYLAND, COLLEGE PARK
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-02-15 至 2015-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8415937
• 关键词: Address; Affect; Anabolism; Antigenic Variation; Bacteria; Biochemical; Biological; Biology; Blood; Cell surface; Cells; Clinical; Collaborations; Data; Disease; Ectopic Pregnancy; Enzymes; Gene Cluster; Gene Structure; Genes; Genetic; Genetic Engineering; Genetic Recombination; Genetic Variation; Genomics; Goals; Gonorrhea; HIV; Health; Health Care Costs; Human; Immune; Infection; Infection Control; Infertility; Invaded; Knowledge; Laboratories; Lead; Modeling; Modification; Molecular; Neisseria gonorrhoeae; Oligosaccharides; Organism; Outcome; Pathogenesis; Pathogenicity; Pelvic Inflammatory Disease; Phase; Play; Positioning Attribute; Prevention; Process; Property; Public Health; Research; Resistance; Role; Serum; Site; Stream; Structure; Surface Antigens; Synovial Fluid; Testing; United States; Vaccines; Variant; Virulence Factors; Woman; base; chronic pelvic pain; cost; design; human tissue; innovation; killings; lacto-N-neotetraose; lipooligosaccharide; novel; novel strategies; pathogen; prevent; tissue culture; tool; transmission process; Address; Affect; Anabolism; Antigenic Variation; Bacteria; Biochemical; Biological; Biology; Blood; Cell surface; Cells; Clinical; Collaborations; Data; Disease; Ectopic Pregnancy; Enzymes; Gene Cluster; Gene Structure; Genes; Genetic; Genetic Engineering; Genetic Recombination; Genetic Variation; Genomics; Goals; Gonorrhea; HIV; Health; Health Care Costs; Human; Immune; Infection; Infection Control; Infertility; Invaded; Knowledge; Laboratories; Lead; Modeling; Modification; Molecular; Neisseria gonorrhoeae; Oligosaccharides; Organism; Outcome; Pathogenesis; Pathogenicity; Pelvic Inflammatory Disease; Phase; Play; Positioning Attribute; Prevention; Process; Property; Public Health; Research; Resistance; Role; Serum; Site; Stream; Structure; Surface Antigens; Synovial Fluid; Testing; United States; Vaccines; Variant; Virulence Factors; Woman; base; chronic pelvic pain; cost; design; human tissue; innovation; killings; lacto-N-neotetraose; lipooligosaccharide; novel; novel strategies; pathogen; prevent; tissue culture; tool; transmission process

DESCRIPTION (provided by applicant): Neisseria gonorrhoeae is responsible for over 1 million cases of gonorrhea each year in the United States. 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. Gonococcal infections can disseminate, from the initial site of infection causing pelvic inflammatory disease (PID), which can lead to tubal infertility, ectopic pregnancy, and chronic pelvic pain, or into the blood stream causing disseminated gonococcal infections (DGI). Lipooligosaccharide (LOS) is a prominent surface antigen and a virulence factor that makes a major contribution to the pathogenesis of these diseases. LOS can exist as multiple chemically related components on a single cell, with variations in the oligosaccharide portion readily interconverting between forms. While one form of this molecule has been extensively studied, there are many other novel structures that are known to exist. The fact that this pathogen possesses so many different ways to manipulate its LOS, and can make such a diversity of structures, indicates that such modifications are important in pathogenesis. The objective of this proposal is to determine the genetic variability associated with LOS biosynthesis and determine if specific LOS structures are associated with specific clinical outcomes of infection by defining the structures expressed by the gonococcus and characterizing the molecular and functional basis for the modulation of the expression of these structures. The central hypothesis of the proposed research is that variation in the biosynthesis of LOS has additional genetic and biochemical underpinnings that have yet to be characterized, and that they lead to the synthesis of additional LOS structures that contribute to different biological properties of the bacterium. I will characterize the structural variability that exists in this species and will use the genetic information obtained to construct strains with invariant defined LOS. I will then analyze the biological significance of these structures by determining their contribution to serum resistance.

描述（由申请人提供）：Neisseria Gonorrhoeae每年在美国负责超过100万例淋病。与治疗淋病相关的医疗保健成本以及由该生物体引起的感染引起的并发症每年超过10亿美元。淋球菌感染可以从引起骨盆炎性疾病（PID）的最初感染部位传播，从而导致输卵管不育症，异位妊娠和慢性骨盆疼痛或引起血液引起的血液，从而导致传播的传播性角球感染（DGI）。脂肪糖（LOS）是一种突出的表面抗原和毒力因子，对这些疾病的发病机理做出了重大贡献。 LOS可以作为单个细胞上的多个化学相关组件存在，其寡糖部分的变化很容易在形式之间互换。尽管已经对该分子的一种形式进行了广泛的研究，但已知存在许多其他新型结构。这种病原体具有操纵其LOS的许多不同方法，并且可以使这种结构多样化，这一事实表明，这种修饰在发病机理中很重要。该提案的目的是确定与LOS生物合成相关的遗传变异性，并通过定义由GONOCOCOCCUS表达​​的结构并表征分子和功能基础来调节这些结构表达的表达，从而确定特定的LOS结构是否与特定的感染临床结果相关。拟议研究的中心假设是，LOS生物合成的变化具有尚未表征的其他遗传和生化基础，并且导致其他LOS结构的综合，这些结构有助于细菌的不同生物学特性。我将表征该物种中存在的结构可变性，并将使用获得的遗传信息来构建具有不变定义的LOS的菌株。然后，我将通过确定它们对血清抗性的贡献来分析这些结构的生物学意义。