COMPLETE GENOME SEQUENCE OF RICKETTSIA TYPHI

将测定和分析伤寒立克次体基因组的完整DNA序列，以确定可能的编码区和基因产物的可能功能。根据《支持大规模基因组测序项目政策》关于潜在生物恐怖主义制剂的增编，伤寒杆菌已被指定为优先生物恐怖主义制剂。这项申请是为了响应这一机会而准备的，以支持将高优先级病原体作为潜在的生物恐怖主义媒介进行大规模基因组测序。伤寒立克次体具有很高的传染性，包括通过气雾剂接触，感染在临床上很难诊断，并导致一种严重的、使人丧失能力的疾病，总死亡率为1%。对其基因组的了解将最有助于与毒力更强的普罗瓦泽克杆菌进行比较，并用于研究毒力因子、减毒目标和潜在的新靶点，这些菌株可以通过基因工程获得对四环素和氯霉素仅有的两种有效药物的抗药性。一旦确定和分析了基因组序列，研究界就可以通过一个带有许多工具的在线数据库获取它们，以方便数据检索。在项目过程中，还将持续发布初步数据。

The complete DNA sequences of the genome of Rickettsia typhi will be determined and analyzed for putative coding regions and possible functions of the gene products. Under an addendum for potential bioterrorism agents of the Policy on Support of Large- Scale Genome Sequencing Projects, R. typhi has been designated as a priority bioterrorism agent. This application is prepared in response to this opportunity for support of large-scale genome sequencing of high priority pathogens as potential agents of bioterrorism. Rickettsia typhi is highly infectious, including via aerosol exposure, infection is deceptively difficult to diagnose clinically and causes a severe, incapacitating illness with 1 percent overall mortality. Knowledge of its genome would be most useful for comparison with that of the more virulent R. prowazekii and for investigation of virulence factors, targets of attenutation, and potential novel targets for antimicrobial therapy of strains that could be engineered to resistance to the only two effective agents, tetracyclines and chloramphenicol. Once the genomic sequences are determined and analyzed they will be made available to the research community through an online database with a number of tools to facilitate data retrieval. During the course of the project there will also be ongoing release of preliminary data.