DNA SEQUENCE OF STAPHYLOCOCCUS AUREUS 8325 GENOME

1995年，Fleischman等人提出。(40)测定了该病毒的核苷酸序列 无预先限制性内切酶切点的流感嗜血杆菌RD 粘粒克隆。这是一个里程碑式的事件，标志着自动DNA 测序和分析已经成熟到强大、高效 有望给生物科学带来革命性变化的技术。一个 将极大地促进结案和证明的重要突破- 对Mike Hunkapiller博士报道的序列的解读 ABI和Roe博士在最近9月份的希尔顿海德DNA测序会议上 会议是我们成功地进行实验的结果 直接从几个碱基中获得超过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 已经或即将完成，包括我们自己的基因组测序 人类重要病原体淋病奈瑟菌和链球菌 化脓性。总的来说，这些研究将大大提高我们的 了解原核生物的分子生物学过程，并提供 基因发现和比较遗传学的新途径。从一个 从实用的角度来看，原核基因组测序将增强我们的 能够理解在致病过程中发生的过程 传染病。这些研究应该提供新的方法来 药物发现，作为微生物越来越重要的必要性 抗生素耐药性威胁着我们治疗细菌的能力 感染。在本应用中，我们建议确定核苷酸 金黄色葡萄球菌基因组序列。这种有机体是一种 广泛存在于人类和动物环境中的强致病菌。它 能够产生超过34种不同的胞外蛋白 其中大部分已被证明在致病中起作用。 生物体或增强毒力。虽然感染的发生率 在一般人口中没有很好的记录，它一般是 承认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外，几乎没有 实际上是金黄色葡萄球菌病的发病机制。 了解控制电路(AGR、SAR和可能的其他电路) 毒力相关基因的表达对理解毒力至关重要。 生物体对宿主产生的信号的遗传反应。我们 建议获取该病毒的基因组序列 金黄色葡萄球菌8325菌株将极大地促进人们对 致病机制由这种有机体产生并与之密切相关的疾病机制 物种。因此，作为一个单一的具体目标，我们将排序和 注释这一重要病原体的2.8Mb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.