MICROBIAL PATHOGEN GENOME PROJECT--NEISSERIA GONORRHOEAE

最近，在方法方面取得了重大进展。 DNA序列的快速测定和分析。然而，重要的是 在对人类进行排序之前，还需要在方法学上取得进展 基因组将被积极追求。相比之下，我们建议当前 方法论显著进步，在分析中大有用处 原核生物基因组，通常大小为1-5兆碱基(Mb)。 确定原核生物基因组的核苷酸序列将 极大地提高了我们了解 该有机体所参与的生物学的遗传学基础。这 努力也将是非常划算的。美国国立卫生研究院有相当大的 对了解许多人类细菌的致病机制感兴趣 感染。因此，我们建议对一种人类细菌病原体进行检测 测试基因组测序是否会增强微生物的致病作用 学习。我们选择淋病奈瑟氏菌作为模式生物， 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发性的。与之形成对比的是 种群具有克隆结构的其他病原体。选择一个 来自泛灵种群的有机体确保了我们不会选择 用于测序的菌株错误，因为所有菌株似乎都具有相同的毒力。 淋球菌(淋球菌)是人类淋病的病原体， 一种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 美国报告了感染病例；这被认为是低估了， 因为少报了。淋病让美国的医疗保健付出了代价 系统每年超过30亿美元。尽管淋球菌感染通常是 被普通公众轻视的这种有机体可以导致严重的疾病， 尤其是在女性身上。女性感染通常是无症状的和 直到出现并发症(盆腔炎和 输卵管炎)出现，造成严重的，通常是永久性的损害 女性生殖道。抗生素耐药性也在不断增加。 担忧。因此，美国国家卫生研究院投入了大量资源用于 了解和控制淋球菌感染。我们建议 测定淋病奈瑟菌FA109O株的核苷酸序列 出于几个原因，FA109O是这些研究的最佳菌株。这 研究是IRPG的一部分，它包括一个配套的应用程序来确定 化脓性链球菌基因组序列测定。科学家们的聚会 在微生物发病机制和基因组测序方面的不同专业知识将 产生协同效应，提供必要的新见解和试剂 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.