BIOSYNTHESIS OF THE MYCOBACTERIAL PEPTIDOGLYCAN

描述(改编自申请者摘要)：结核病是 成人死亡的主要原因是一种感染性有机体。到年底的时候 本世纪可能有多达9000万新的结核病病例。 导致多达3000万人死亡。抗菌治疗的失败和 结核病和艾滋病之间的危险联系重新带来了 对研究结核分枝杆菌的兴趣，结核分枝杆菌是导致这一现象的微生物 疾病。更好地了解生物体的基本生物学和 开发新的抗分枝杆菌药物是 分枝杆菌研究。在以下情况下，细胞包膜是一个突出的特征 分枝杆菌，由多种多糖组成，如 阿拉伯半乳聚糖、阿拉伯甘露脂和肽聚糖，以及几种 不同类型的脂类，包括各种糖脂和真菌酸。 细胞包膜的肽聚糖层作为 细胞包膜的主要成分，并提供形状和结构 对细胞的完整性。这项提议的长期目标是更深层次的 了解分枝杆菌细胞的生物合成和组装 信封。这项建议的具体目标是更多地了解 包膜的肽聚糖层的遗传学和生物合成。这个 这项建议的具体目的是：1)确定 分枝杆菌肽聚糖的N-糖基化。2)调查 肽聚糖的结构及其在组织中的作用 手机信封。3)以β-内酰胺类抗生素为工具 分枝杆菌肽多糖的生物合成。就这项提案的目标而言，国际和平研究所 将研究结核分枝杆菌和污垢分枝杆菌作为模式生物 经典细菌遗传学、分子生物学和生物化学技术。

DESCRIPTION (Adapted from the Applicant's Abstract): Tuberculosis is the leading cause of death in adults due to an infectious organism. By the end of this century there may be as many as 90 million new cases of tuberculosis resulting in up to 30 million deaths. The failure of antimicrobial therapy and the dangerous association between tuberculosis and AIDS have brought renewed interest in studying M. tuberculosis, the organism responsible for this disease. A better understanding of the basic biology of the organism and the development of new anti-mycobacterial drugs are important goals of mycobacterial research. The cell envelope is an outstanding characteristic if the mycobacteria, consisting of a variety of polysaccharides such as arabinogalactan, lipoarabinomannan, and peptidoglycan, along with several different types of lipids including various glycolipids and the mycolic acids. The peptidoglycan layer of the cell envelope serves as the anchor for the principal components of the cell envelope and provides shape and structural integrity to the cell. The long-term goal of this proposal is a deeper understanding of the biosynthesis and assembly of the mycobacterial cell envelope. The specific goal of this proposal is to understand more about the genetics and biosynthesis of the peptidoglycan layer of the envelope. The specific aims of this proposal are: 1) Determining the significance of N-glycolylation of the mycobacterial peptidoglycan. 2) Investigating the architecture of the peptidoglycan and the role it plays in the organization of the cell envelope. 3) Using beta-lactam antibiotics as tools to probe mycobacterial peptidoglycan biosynthesis. For the aims of this proposal, the Pi will study M. tuberculosis and M. smegmatis as a model organism using the techniques of classical bacterial genetics, molecular biology and biochemistry.