INTEGRATION AND EXCISION OF PROPHAGES IN TUBERCULOSIS

描述（改编自申请人摘要）：结核分枝杆菌 感染导致的死亡人数比任何其他单一传染性病原体都多。超过 在过去的十年里，遗传学方法取得了重大进展， 分枝杆菌的解剖和最近的完整描述 基因组测序将加速新药、更好的疫苗和 更快速的诊断方法。然而，M.结核 发病机制，耐药机制，中枢代谢过程 以及M.结核病与其宿主， 明白噬菌体在其宿主的生物学中起着核心作用。 它们不仅介导细菌菌株之间的遗传交换， 与细菌毒力的决定因素密切相关。比如说， 它们经常编码毒素或其他影响病原体的因子， 细菌宿主的特性。分枝杆菌噬菌体的研究也 为M.结核病和新工具 用于其分析。分枝杆菌基因组结核杆菌含有两个类原噬菌体 元素phiRv 1和phiRv 2。然而，这些不是典型的预言， 它们都相当小长度小于10 kb并且不包含完整的 病毒繁殖所需基因的互补。然而，他们两人 似乎有完整的重组机制，一个是有关的 整合酶系统，以及含有新的 解离酶样重组酶。因此，虽然这些预言可能不会单独拥有 可能产生感染性病毒颗粒，它们可能是移动的， 可以在基因组中进出。在本研究中，PI将调查 M.以确定他们是否患有结核病 功能重组系统;它们是否作为遗传转移剂; 以及它们是否在M.结核

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.