DNA SEQUENCE OF STAPHYLOCOCCUS AUREUS 8325 GENOME

1995年，Fleischman等人（40）确定了 事先未进行限制性酶切位点作图的流感嗜血杆菌Rd， 粘粒克隆 这是一个里程碑式的事件，标志着自动化DNA 测序和分析已经成熟到强大、高效、 有望彻底改变生物科学的技术。 一个 这是一个重大突破，将大大促进关闭和证明- 阅读序列，由Mike Hunkapiller博士报告， ABI和Roe博士在最近九月的希尔顿头部DNA测序 会议是实验的结果，我们成功地 直接从几个序列中获得了超过450个碱基的序列数据， 细菌基因组 其他几种原核生物的基因组序列 包括我们自己的基因组测序 淋病奈瑟氏菌和链球菌 化脓总的来说，这些研究将大大提高我们的 了解原核分子生物学过程，并提供 基因发现和比较遗传学的新途径。从 从实用的角度来看，原核基因组测序将提高我们的 理解发病过程中发生的过程的能力 传染病 这些研究将为以下方面提供新的方法： 药物发现，作为微生物， 抗生素耐药性威胁着我们治疗细菌性疾病的能力， 感染. 在本申请中，我们建议测定核苷酸 金黄色葡萄球菌的基因组序列。 这种生物是一种 广泛存在于人类和动物环境中的强效病原体。 它 能够产生多达34种不同的细胞外蛋白质 其中大多数已被证明在致病性中发挥作用， 生物体或增强毒性。 尽管感染的发生率 在一般人群中没有很好的记录，通常 承认S。金黄色葡萄球菌占所有医院感染的三分之一 菌血症 除了脓肿形成的细节，很少 实际上是葡萄球菌病的发病机制。 了解控制电路（agr，sar和其他） 毒力相关基因的表达对于理解 生物体对宿主产生的信号的遗传反应。 我们 建议获得的基因组序列的基因组， 金黄色葡萄球菌菌株8325将极大地促进理解 这种生物体产生疾病的机制及其密切相关 物种 因此，作为一个单一的具体目标，我们将排序， 注释这一重要病原体的2.8 Mb基因组。

In 1995, Fleischman et al. (40) determined the nucleotide sequence of Haemophilus influenzae Rd without prior restriction site mapping and cosmid cloning. This was a landmark event, signaling that automated DNA sequencing and analysis have matured into robust, highly efficient technologies promising to revolutionize the biological sciences. An important breakthrough that will greatly facilitate closure and proof- reading of the sequence which was reported by Dr. Mike Hunkapiller from ABI and Dr. Roe at the recent September Hilton Head DNA Sequencing conference was the results of experiments in which we successfully obtained sequence data in excess of 450 bases directly from several bacterial genomes. The genomic sequence of several other procaryotes have or will be completed shortly, including our own genomic sequencing of the important human pathogens Neisseria gonorrhoeae and Streptococcus pyogenes. Collectively, these studies will considerably enhance our understanding of procaryotic molecular biological processes, and provide new avenues for gene discovery and comparative genetics. From a practical standpoint, procaryotic genome sequencing will enhance our ability to understand processes occurring during the pathogenesis of infectious disease. These studies should provide new approaches for drug discovery, a necessity of increasing importance as microbial antibiotic resistance threatens our ability to treat bacterial infections. In this application, we propose to determine the nucleotide sequence of the genome of Staphylococcus aureus. This organism is a potent pathogen widely found in the human and animal environment. It is capable of producing upwards of 34 different extracellular proteins most of which have been shown to play a role in the pathogenicity of the organism or to enhance virulence. Although the incidence of infection in the general population is not well documented, it is generally accepted that S. aureus accounts for up to one-third of all nosocomial bacteremia. Other than the details of abscess formation, very little is actually of the pathogenesis of staphylococcal disease. Understanding the circuits (agr, sar and probably others) which control the expression of virulence related genes is paramount to understanding the genetic response of the organism to host generated signals. We propose that acquisition of the sequence of the genome of the Staphylococcus aureus strain 8325 will greatly facilitate understanding the mechanism of disease produced by this organism and closely related species. Therefore, as a single specific aim, we will sequence and annotate the 2.8 Mb genome of this important pathogen.