GENES ASSOCIATED WITH M AVIUM PATHOGENESIS

描述：(改编自申请人摘要)属于 艾滋病患者的感染情况。与非艾滋病人相比，在艾滋病 患者禽类分枝杆菌主要通过胃肠道获得。 肠道定植后，禽类分支杆菌侵入肠道。 继发性感染粘膜下巨噬细胞和单核细胞。一次 在巨噬细胞内，禽类分枝杆菌抑制酸化和成熟 吞噬小体，为复制和生存创造条件，并随后 传播。与侵袭和细胞内相关的基因 存活是鸟型支原体致病的关键。然而，到目前为止，只有少数几个 目前已鉴定出鸡传染性支气管炎病毒的毒力基因。申请者 提议开发能够识别基因的遗传系统 与毒力有关的病毒。更具体地说，他们将发展 禽类分枝杆菌的遗传系统：1.分离和新的毒力决定因素 与肠上皮内的结合、侵袭和持久性有关 转座子突变和报告基因系统在细胞和巨噬细胞中的应用 2对已鉴定的可能毒力基因进行敲除突变。这个 研究人员计划将他们的努力集中在之前描述的两个基因上， 苏打水和法巴。3.对所产生的突变进行互补以恢复 致命性。申请人认为，本提案中概述的研究 将为鉴定新的相关基因提供极好的工具 并对其致病机理进行了初步探讨。

DESCRIPTION: (Adapted from Applicant's Abstract) Organisms belonging to the infection in patients with AIDS. In contrast with non-AIDS individuals, in AIDS patients M. avium is primarily acquired through the gastrointestinal tract. Following colonization of the intestines, M. avium invades the intestinal mucosa and secondarily infects submucosal macrophages and monocytes. Once within macrophages, M. avium inhibits acidification and maturation of phagosomes, creating conditions for replication and survival, and subsequently dissemination. The genes which are associated with invasion and intracellular survival are keys for M. avium pathogenesis. However, thus far only a few putative virulence genes have been identified on M avium. The applicants propose to develop genetic systems that will allow the identification of genes that are associated with virulence. More specifically, they will develop genetic systems in M. avium for: 1. Isolation and novel virulence determinants associated with binding, invasion and persistence within intestinal epithelial cells and macrophages using transposon mutagenesis and reporter gene systems 2 knockout mutagenesis of previously identified putative virulence genes. The investigators plan to focus their effort on two previously described genes, sodA and fapA. 3. Complementation of the resulting mutation to restore virulence. The applicants believe that the studies outlined in this proposal will provide excellent tools for the identification of novel genes associated with mechanisms of pathogenesis of M. avium.m.