MYCOBACTERIOPHAGE L5 AS A TOOL BOX FOR TUBERCULOSIS

噬菌体 L5 作为结核病的工具箱

• 批准号: 2057348
• 负责人: Graham F. Hatfull
• 金额: $ 7.18万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-02-01 至 1999-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2057348
• 关键词: Bacillus Calmette Guerin vaccine; Mycobacterium tuberculosis; bacterial genetics; bacterial virus; gene expression; genetic manipulation; genetic promoter element; genetic regulation; luciferin monooxygenase; luminescence; lysogeny; reporter genes; tuberculosis; virus infection mechanism

Approximately one-third of the world's population is infected with Mycobacterium tuberculosis, the causative agent of tuberculosis. While the majority of these infections do not progress immediately to active disease, tuberculosis results in about 3 million deaths each year. In the United States, there has been a significant increase in the incidence of tuberculosis in recent years, in large part due to an increase in HIV infection. This increase is accompanied by the alarming appearance of drug resistant and multiple drug resistant strains of tuberculosis. There is clearly a need for new antituberculosis drugs, better and more effective vaccines and rapid methods for diagnosis and drug susceptibility determination. Effective control of tuberculosis requires an understanding of the genetic basis of M. tuberculosis virulence, mechanisms of gene expression and its regulation, and specific tools for the genetic manipulation of the mycobacteria. However, it is only very recently that a genetic system for mycobacteria has been established and these questions have yet to be fully addressed. Viruses have proven to be valuable aids in the exploration of a variety of organismal genetic systems. It is expected that a study of mycobacterial viruses will both enhance our understanding of mycobacterial genetics and provide tools for genetic manipulation of pathogenic mycobacteria. Previous studies have established mycobacteriophage L5 as the best characterized of the mycobacterial viruses and validated the utility of this approach. This project proposes to elucidate the mechanisms of gene expression and regulation in L5 and its mycobacterial hosts; this information will be used for the construction of novel diagnostic luciferase reporter phages and to provide tools for the construction of recombinant antituberculosis vaccines. These studies will also contribute to the repertoire of tools available for genetic manipulation of the mycobacteria.

大约三分之一的世界人口感染 结核分枝杆菌，结核病的病因。而 这些感染中的大多数不会立即发展 疾病，结核病每年约300万人死亡。在 美国，发病率已大大增加 近年来结核病，很大程度上是由于HIV增加 感染。这种增加伴随着毒品的惊人外观 结核病的抗性和多种耐药菌株。有 显然需要新的抗结核药物，更有效，更有效 疫苗和诊断和药物敏感性的快速方法 决心。 有效控制结核病需要了解遗传 结核分枝杆菌毒力，基因表达机制及其基础 调节以及用于遗传操纵的特定工具 分枝杆菌。但是，直到最近才是一个遗传系统 已经建立了分枝杆菌，这些问题尚未完全 解决。 事实证明，病毒是探索各种的宝贵辅助 有机遗传系统。预计分枝杆菌的研究 病毒既会增强我们对分枝杆菌遗传学的理解，又会增强我们的理解 提供用于致病性分枝杆菌基因操纵的工具。 先前的研究已将分枝杆菌L5确定为最好的 以分枝杆菌病毒为特征，并验证了 这种方法。 该项目建议阐明基因表达的机制和 L5及其分枝杆菌宿主的调节；这些信息将是 用于构建新型诊断荧光素酶报告基因噬菌体 并提供建造重组抗结核的工具 疫苗。这些研究还将有助于工具的曲目 可用于分枝杆菌的基因操纵。