MICROBIAL PATHOGEN GENOME PROJECT--NEISSERIA GONORRHOEAE

最近，在计算方法方面取得了重大进展， DNA序列的快速测定和分析。然而，重要的 在人类基因组测序之前， 基因组将被积极追求。 相比之下，我们建议， 方法论是显著先进的，在分析中非常有用 原核生物基因组，其大小通常为1-5兆碱基（Mb）。 确定原核基因组的核苷酸序列将 极大地提高了我们理解 生物体参与的生物学的遗传基础。这 “奋进”也将具有极高的成本效益。国家卫生研究院有一个相当大的 有兴趣了解许多人类细菌的发病机制 感染.因此，我们建议检查人类细菌病原体， 测试基因组测序是否会增强微生物的致病性 问题研究我们选择淋病奈瑟菌作为该模式生物， 有几个原因最重要的是，最近的数据表明，N。 淋病的种群结构是泛繁殖的。与几个不同 其他病原体，其种群具有克隆结构。选择一个 一个来自全交配种群的生物确保了我们不会挑选 测序的错误菌株，因为所有菌株似乎具有相同的毒力。 N.淋病（淋球菌）是人类淋病的病原体， 对健康有重大影响的性传播疾病， 美国民众的福祉。通常，100万或更多的淋球菌 在美国报告了感染;这被认为是低估了， 因为少报。淋球菌疾病花费了美国的医疗保健 系统每年超过30亿美元。虽然淋球菌感染通常 这种微生物被普通大众所轻视，但却能引起严重的疾病， 尤其是女性。妇女感染往往无症状， 未确诊，直到并发症（盆腔炎和 输卵管炎）出现，造成重大的，往往是永久性的损害， 女性生殖道抗生素耐药性也在增加 关心因此，NIH投入了大量资源， 了解和控制淋球菌感染。我们建议 测定了N.淋病菌株FA 109 O;用于 出于多种原因，FA 109 O是这些研究的最佳菌株。这 研究是IRPG的一部分，其中包括一个配套应用程序来确定 化脓性链球菌的基因组序列 科学家的集会 在微生物发病机理和基因组测序方面的各种专业知识将 产生协同作用，将提供新的见解和必要的试剂 用于研究这些医学上重要的微生物。

Recently, significant progress has been made in the methodology for the rapid determination and analysis of DNA sequence. However, significant gains in methodology need yet be made before sequencing of the human genome will be aggressively pursued. By contrast, we propose that current methodology is significantly advanced to be of great use in the analysis of prokaryotic genomes, which are commonly 1-5 megabases (Mb) in size. Determining the nucleotide sequence of a prokaryotic genome will dramatically enhance the rate at which we will come to understand the genetic basis for the biology in which that organism participates. This endeavor will also be extremely cost-effective. The NIH has a considerable interest in understanding the pathogenesis of many human bacterial infections. Therefore, we propose to examine a human bacterial pathogen to test whether genomic sequencing will enhance microbial pathogenesis studies. We have selected Neisseria gonorrhoeae as this model organism, for several reasons. Most importantly recent data indicates that N. gonorrhoeae population structure is panmictic. in contrast to several other pathogens whose populations have a clonal structure. Selecting an organism from a panmictic population ensures that we will not pick the wrong strain for sequencing, as all strains appear of equivalent virulence. N. gonorrhoeae (the gonococcus) is the causative agent of human gonorrhea, a sexually transmitted disease with significant impact on the health and well-being of the U.S. populace. Typically, 1 million or more gonococcal infections are reported in the U.S.; this is considered an underestimate, due to underreporting. Gonococcal disease costs the U.S. health care system over $3 billion annually. Although gonococcal infections are often trivialized by the lay public, the organism can cause severe disease, particularly in women. Infections in women are often asymptomatic and undiagnosed until complications (pelvic inflammatory disease and salpingitis) appear, causing significant and often permanent damage to the female reproductive tract. Antibiotic resistance is also of increasing concern. Consequently, the NIH has devoted significant resources for understanding and controlling gonococcal infections. We propose to determine the nucleotide sequence of N. gonorrhoeae strain FA109O; for several reasons, FA109O is the optimal strain for these studies. This study is part of IRPG that includes a companion application to determine the genome sequence of Streptococcus pyogenes. The assembly of scientists and varied expertise in microbial pathogenesis and genomic sequencing will produce a synergy that will provide new insights and reagents essential for the study of these medically important microorganisms.