STUDIES ON AIDS-RELATED OPPORTUNISTIC PATHOGEN

虽然禽分枝杆菌复合体在临床上代表了一种 艾滋病病原体中重要的机会性病原体 患者，缺乏关于其致病性的信息 产生了一个关键的科学空白，使得很难治疗 涉及这些微生物的感染。这个问题已经恶化了 最近以NIH研讨会和巴斯德研究所的形式受到关注 旨在确定和讨论重要的高优先级领域的论坛 对这些重要的机会性病原体的理解。这个 这项研究提案的长期目标是形成一种协作 这一努力将导致更好地理解三个重要的 已经为禽类分枝杆菌复合体、致病性、 毒力和多重耐药性。这将通过以下方式实现 结合了两个研究过这些问题的实验室的努力 分枝杆菌在过去的几年里。具体目标将是 为了阐明定义血清变种作用的基本机制- 糖肽脂(GPL)特异性抗原在致病中的作用 研究GPL的生物合成，以便特定的代谢 最终可以确定靶点以改善抗分枝杆菌 心理治疗。除了最初为期六个月的访问外，还有两次为期三个月的访问 请拨下列两年期间的经费。目的 这两次访问是为了完成将在 最初为期六个月的研究。这些单独的访问将主要处理 1)未提纯的新的禽类分枝杆菌脂类的分析 在第一次访问的时间内提供足够的数量；2) 药物引起的潜在脂质前体的鉴定 抑制性研究。

Although the Mycobacterium avium complex represents a clinically significant group of opportunistic pathogens in AIDS pathogens in AIDS patients, the lack of information regarding their pathogenicity has generated a critical scientific void that makes it difficult to treat infections involving these microorganisms. This problem has gained recent attention in the form of NIH Workshops and Institute Pasteur Forums designed to identify and discuss high-priority areas important in the understanding of these significant opportunistic pathogens. The long-term objective of this research proposal is to form a collaborative effort that will result in a better understanding of three important areas that have been defined for the M. avium complex, pathogenicity, virulence and multiple drug resistance. This will be accomplished by combining the efforts of two laboratories that have studied these mycobacteria throughout the last several years. Specific aims will be to elucidate the basic mechanisms that define the role of the serovar- specific glycopeptidolipid (GPL) antigens in pathogenicity and to investigate the biosynthesis of the GPL so that specific metabolic targets can eventually be identified to improve antimycobacterial therapy. In addition to the initial six-month visit, two 3-month visits are being requested for the following two year periods. The purpose of these two visits is to complete work that will be started during the initial six-month study. These separate visits will deal primarily with 1) the analysis of new M. avium lipids that will have not been purified in sufficient quantities in time for the first visit and 2) the identification of potential lipid precursors that result from drug inhibitory studies.