GENES ASSOCIATED WITH M AVIUM PATHOGENESIS

描述：（改编自申请人的摘要） 感染艾滋病的病人。与非艾滋病患者相比， 患者M.禽流感主要通过胃肠道获得。 在肠道定植后，M.禽侵肠 感染粘膜，并继发感染粘膜下巨噬细胞和单核细胞。一旦 巨噬细胞内M. avium抑制酸化和成熟 吞噬体，为复制和生存创造条件， 传播。与侵袭和细胞内 生存是M的关键。鸟类致病机理然而，到目前为止， 已经在M avium上鉴定了推定的毒力基因。申请人 建议开发遗传系统， 与毒力有关更具体地说，他们将开发 遗传系统在M. Avium for：1.分离和新的毒力决定因子 与肠上皮内的结合、侵袭和持久性相关 使用转座子诱变和报告基因系统的细胞和巨噬细胞 2先前鉴定的推定毒力基因的敲除诱变。的 研究人员计划将他们的精力集中在两个先前描述的基因上， sodA和fapA。3.互补产生的突变以恢复 毒性申请人认为，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， 探讨了M. avium.m.

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.