COMPLETE GENOME SEQUENCE OF RICKETTSIA TYPHI

对斑疹立克次体基因组的完整DNA序列进行测定和分析，以推测编码区和基因产物的可能功能。在支持大规模基因组测序计划政策的潜在生物恐怖制剂附录中，伤寒杆菌被指定为优先生物恐怖制剂。本申请是为了响应这一机会而准备的，以支持作为生物恐怖主义潜在代理人的高优先级病原体的大规模基因组测序。伤寒立克次体具有高度传染性，包括通过气溶胶接触，感染在临床上很难诊断，并导致严重的致残疾病，总死亡率为1%。对其基因组的了解将有助于与毒性更强的普拉兹基氏r.p awazekii进行比较，并有助于研究毒力因子、减毒靶点，以及对菌株进行抗菌治疗的潜在新靶点，这些菌株可以被设计成对仅有的两种有效药物——四环素和氯霉素产生耐药性。一旦基因组序列被确定和分析，它们将通过一个带有许多工具的在线数据库提供给研究界，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.