INTEGRATION AND EXCISION OF PROPHAGES IN TUBERCULOSIS

描述(改编自申请者摘要)：结核分枝杆菌 感染导致的死亡比任何其他单一的传染病病原体都要多。完毕 在过去的十年里，遗传研究方法取得了实质性的进展。 分枝杆菌的解剖和完整的最新描述 基因组序列将加速发现新药、更好的疫苗和 更快速的诊断方法。然而，结核分枝杆菌的分子基础 发病机制、耐药机制、中枢代谢过程 以及结核分枝杆菌与其宿主的关系仍然很差 明白了。噬菌体在宿主的生物学中起着核心作用。 它们不仅调节细菌菌株之间的遗传交换，而且它们还 与细菌毒力的决定因素密切相关。例如, 它们经常编码毒素或其他影响致病因子的因素 细菌宿主的性质。分枝杆菌噬菌体研究也 提供了对结核分枝杆菌生物学和新工具的大量见解 以供其分析。结核分枝杆菌基因组包含两个类似于原噬菌体的 元素phiRv1和phiRv2。然而，这些并不是典型的先知 它们都相当小-长度不到10kb-并且不包含完整的 病毒繁殖所需的基因互补。尽管如此，他们都 似乎有完整的重组机制，其中一个与 分枝杆菌噬菌体L5的整合酶系统及其包含一种新的 类分解酶重组酶。因此，虽然这些先知可能并不是唯一拥有 有可能产生传染性病毒颗粒，它们很可能是可移动的 可能会在基因组中进出。在这项研究中，私家侦探将调查 结核分枝杆菌噬菌体样元件的检测 功能重组系统；它们是否作为遗传转移剂； 以及它们是否在结核分枝杆菌的毒力中发挥作用。

DESCRIPTION (Adapted from the Applicant's Abstract): Mycobacterium tuberculosis infections result in more deaths than any other single infectious agent. Over past ten years, substantial advances have been made in methods for the genetic dissection of the mycobacteria and the recent description of the complete genome sequence will expedite the discovery of new drugs, better vaccines and more rapid diagnostic methods. however, the molecular basis of M. tuberculosis pathogenesis, the mechanism of drug resistance, the central metabolic processes and the relationship of M. tuberculosis with its host, remain poorly understood. Bacteriophages play central roles in the biology of their hosts. Not only do they mediate genetic exchange among bacterial strains but they also are closely associated with determinants of bacterial virulence. For example, they frequently encode toxins or other factors that influence the pathogenic properties of the bacterial host. Mycobacterial phage studies have also provided numerous insights into the biology of M. tuberculosis and novel tools for its analysis. The genome of M. tuberculosis contains two prophage-like elements phiRv1 and phiRv2. However, these are not typical prophages in that they are both rather small-less than 10 kb in length-and do not contain a full complement of the genes needed for viral propagation. Nevertheless, they both appear to have intact recombination machineries, one that is related to the integrase system of mycobacteriophage L5, and one that contains a novel resolvase-like recombinase. Thus, while these prophages may not alone have the potential to generate infectious viral particles, they are probably mobile and may move in and out of the genome. In this study, the PI will investigate the prophage-like elements of M. tuberculoses to determine whether they have functional recombination systems; whether they act as Genetic Transfer Agents; and whether they play a role in virulence of M. tuberculosis.