WHOLE GENOME SEQUENCING OF COXIELLA BURNETTI

人畜共患病Q热是由伯氏柯克斯体细胞内专性细菌引起的。伯氏柯克斯体已经进化出在充满敌意的吞噬体体环境中生存的策略。该试剂对于发展细菌致病策略的比较视角是重要的。大多数病原体要么不能在环境中长时间存活，要么像许多革兰氏阳性病原体一样，进化出产孢子的能力，以生存长时间的脱水。伯氏柯克斯体是一种革兰氏阴性菌，它已经开发出一种新的、不产生孢子的策略，以非复制型形式长期生存。这一特性导致了这种病原体被认为是一种生物战剂。它在环境中的稳定性引起了负责规划对非法释放该制剂的反应的官员的严重关切。全基因组序列的阐明将为治疗干预的设计提供重大突破，并为其生物学提供独特的视角。我们建议对伯氏柯克斯体9英里第I期(RSA493)的2.1MBP基因组进行测序，因为它具有已知的毒力潜力，并随后可能与其他分离组进行比较。基因组测序将通过TIGR目前使用的全基因组随机散弹枪测序来完成。此外，基因组将通过计算机技术进行注释，以识别所有开放阅读框(ORF)，并尽可能多地将ORF与已知功能的蛋白质联系起来。

The zoonotic disease Q fever is a caused by the obligate intracellular bacterium Coxiella burnetii. Coxiella burnetii has evolved strategies to survive in the hostile phagolysosomal environment. This agent is important for developing a comparative perspective on bacterial pathogenesis strategies. Most pathogens either do not survive extended periods in the environment or, like many Gram-positive agents, have evolved the ability to sporulate to survive long periods of dessication. Coxiella burnetii is a Gram-negative organisms that has developed a novel, non-sporulating strategy to survive in a non-replicative form for long periods. This property has lead to the consideration of this pathogen as a bio-warfare agent. Its stability in the environment presents a serious concern for officials responsible for planning a response to the illegitimate release of this agent. Elucidation of the complete genomic sequence would provide a major breakthrough in the design of therapeutic intervention and a unique perspective on its biology. We propose to sequence the 2.1 Mbp genome of Coxiella burnetii Nine Mile, phase I (RSA 493) because of its known virulence potential and subsequent potential for comparison with other isolate groups. The genome sequence will be accomplished by the whole genome random shotgun sequencing currently used at TIGR. Additionally, the genome will be annotated by computer techniques to identify all open reading frames (ORFs) and relate as many ORFs as possible to proteins of known function.