GENES ASSOCIATED WITH M AVIUM PATHOGENESIS

与 M AVIUM 发病相关的基因

• 批准号: 6373844
• 负责人: Luiz Eduardo Bermudez
• 金额: $ 29.44万
• 依托单位: CALIFORNIA PACIFIC MED CTR RES INSTITUTE
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-08-01 至 2002-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6373844
• 关键词: Animalia; Mycobacterium avium; bacterial genetics; cell line; gastrointestinal epithelium; gene complementation; gene targeting; green fluorescent proteins; intestinal mucosa; molecular cloning; mutant; plasmids; reporter genes; transposon /insertion element; virulence

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.

描述：（改编自申请人的摘要） 艾滋病患者的感染。与非辅助人员相反，在艾滋病中 患者主要是通过胃肠道获得的。 肠道定植后，鸟枝侵入肠道 粘膜和第二感染粘膜下巨噬细胞和单核细胞。一次 在巨噬细胞中，鸟杆菌抑制酸化和成熟 吞噬体，创造复制和生存的条件，然后 传播。与侵袭和细胞内有关的基因 存活是M. avium发病机理的钥匙。但是，到目前为止只有少数 假定的毒力基因已在M avium上鉴定出来。申请人 提议开发遗传系统，以识别基因 与毒力有关的。更具体地说，他们会发展 M. Avium中的遗传系统：1。隔离和新型毒力决定因素 与肠上皮内的结合，侵袭和持久性有关 细胞和巨噬细胞使用转座子诱变和报告基因系统 2先前鉴定的推定毒力基因的敲除诱变。这 调查人员计划将精力集中在先前描述的基因上， 苏打和FAPA。 3。互补以恢复的突变 毒力。申请人认为，该提案中概述的研究 将为识别相关的新基因提供出色的工具 带有大鸟杆菌发病机理的机制。