GLYCOPEPTIDOLIPID BIOSYNTHESIS IN M AVIUM COMPLEX

M AVIUM 复合物中糖肽脂的生物合成

• 批准号: 3145190
• 负责人: William W Barrow
• 金额: $ 0.26万
• 依托单位: UNIVERSITY OF NORTH TEXAS HLTH SCI CTR
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-08-01 至 1994-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3145190
• 关键词: Mycobacterium avium; aminoacid analog; avidin; carbohydrate analog; cell free system; cell wall; glycolipids; lipid biosynthesis; microorganism growth; microorganism metabolism; opportunistic infections; radiotracer

The clinical management of acquired immune deficiency syndrome (AIDS) is more difficult because of opportunistic infections, the more serious of which are those involving members of the Mycobacterium avium complex. Because members of the M. avium complex are resistant to most antimycobacterial drugs, therapy usually involves 4-6 drugs and prognosis is poor. Because of the strategic location of the glycopeptidolipid antigens (GPL) in the cell wall and the fact that they are unique to members of the M. avium complex, inhibition of GPL biosynthesis should lead to a selective means of treating infections caused by these organisms. Previous studies in this laboratory have lead to the isolation of rough-colony M. avium complex variants and the development of radiolabeling techniques which can be used to study the biosynthesis of the GPL components and related precursors. The long term objective of this research proposal is to investigate the biosynthetic pathway of the GPL in an effort to identify metabolic targets for selective antimicrobial activity. The immediate objective will be to identify potential precursors in GPL biosynthesis and utilize those precursors in a cell-free system to further delineate the biosynthetic pathway of the GPL components. Two approaches will be taken to identify the potential precursors. In the first approach mycobacteria will be treated with drugs which have the potential to inhibit GPL biosynthesis and radiolabeling techniques will be used to identify concomitant accumulation of radiolabeled precursors. In the second approach, rough-colony variants, which lack the ability to complete the synthesis of GPL components but contain initial products of GPL synthesis, will also be used to identify potential precursors. Ability of the potential precursors to participate in GPL biosynthesis will be confirmed by using a cell-free system which has been developed to study in vitro biosynthesis of GPL components. Once the precursors have been confirmed, then the cell-free system will be utilized to examine the effect of specific inhibitors on GPL biosynthesis. These studies should eventually lead to the identification of key enzymes in the GPL biosynthetic pathway, thus making it possible to develop selective antimicrobial therapy for treating M. avium complex infections.

获得性免疫缺陷综合征的临床处理 （艾滋病）是更困难的，因为机会性感染， 其中更严重的是涉及 鸟分枝杆菌复合体。 因为M.鸟 复合体对大多数抗分枝杆菌药物、治疗 通常涉及4-6种药物，预后较差。 因为 糖肽脂抗原（GPL）在 细胞壁和事实，他们是唯一的成员的M。 鸟复合物，抑制GPL生物合成应导致 选择性地治疗由这些生物体引起的感染的方法。 该实验室以前的研究已经导致分离出 粗菌落M. avium复杂的变种和发展 放射性标记技术，可用于研究 GPL组分和相关前体的生物合成。 的 这项研究的长期目标是调查 GPL的生物合成途径，以确定代谢 选择性抗微生物活性的目标。 立即 目标是确定GPL中的潜在前体 生物合成并在无细胞系统中利用这些前体， 进一步描述GPL组分的生物合成途径。 将采取两种方法来确定潜在的前兆。 在第一种方法中，分枝杆菌将用药物治疗， 具有抑制GPL生物合成和放射性标记的潜力 技术将被用来确定伴随的积累 放射性标记的前体。 在第二种方法中，粗糙集落 变体，缺乏完成GPL合成的能力 成分，但包含GPL合成的初始产物，也将 用于识别潜在的前体。 潜力能力 参与GPL生物合成的前体将通过 使用无细胞系统，该系统已被开发用于体外研究 GPL组分的生物合成。 一旦前体被 确认，然后将利用无细胞系统来检查 特异性抑制剂对GPL生物合成的影响。 这些 这些研究最终将导致确定关键酶 在GPL生物合成途径，从而使其有可能开发 选择性抗菌治疗M.鸟分枝杆菌复合体 感染.