BIOSYNTHESIS OF BACTERIAL CELL WALL COMPONENTS

细菌细胞壁成分的生物合成

• 批准号: 3124197
• 负责人: FRANCIS C NEUHAUS
• 金额: $ 20.03万
• 依托单位: NORTHWESTERN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1979
• 资助国家: 美国
• 起止时间: 1979-05-01 至 1993-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3124197
• 关键词: affinity labeling; alanine; aminoacyltransferase; antibacterial agents; binding proteins; cell wall; chemical structure function; crosslink; drug metabolism; electron microscopy; enzyme induction /repression; enzyme mechanism; esterification; gram positive bacteria; immunofluorescence technique; lipid bilayer membrane; membrane activity; membrane lipids; membrane proteins; membrane reconstitution /synthesis; membrane structure; microorganism metabolism; mutant; penicillins; peptidoglycan; secretion; teichoate; transacylation

The primary aim of our research plan is directed towards an understanding of cell wall biosynthesis on the molecular level. This research will provide insights into the processing of peptidoglycan (PG), the mechanism of penicillin action, dynamics of the assembly processes, levels of lipid bilayer organization, and the biosynthesis and function of lipoteichoic acid. Five specific aims will be investigated. (1) It is our hypothesis that the cross-linking of PG in Gaffkya homari occurs by a pathway that requires a penicillin-sensitive N- acetylmuramyl-L-alanine amidase and a penicillin-insensitive transpeptidase. To support this hypothesis, it is our aim to isolate the amidase from this organism and relate this enzyme to PBP-6, the primary in vivo target of penicillin. (2) Penicillin also causes the enhanced secretion of water-soluble PG, lipids, LTA and proteins. It is our aim to establish the mechanisms of the penicillin-induced release of these compounds. (3) The intramembranal mechanism of peptidoglycan formation is not well understood. It is our goal to use probe-labeled lipid intermediates to study the dynamics of the assembly process, the formation of lipid oligomers, and the membrane proteins in the assembly complex. (4) Lipid bilayer organization plays an important role in the assembly of PG. It is our aim to develop an understanding of the organization that is responsible for the association of membrane and wall, and the organization of the PG assembly complex. (5) The D-alanyl esters of lipoteichoic acid appear to play a vital function in cell division and separation. It is our aim to establish the molecular events required for the incorporation of D-alanine and the transacylation of the D-alanyl ester residues. Transacylation of these esters on the poly(glycerophosphate) moiety may represent a unique way of transmitting a signal from one location in the membrane to another. The effects of antibiotics, e.g. penicillin, on well-characterized assembly systems is instrumental to our definition of their mechanisms of action. As new target sites are described n these systems, it is proposed that novel types of antibacterial agents may be designed. D-Alanyl-lipoteichoic acid has been implicated in a variety of bacterial adhesion processes involved in the infectious process. This property may be modulated in part by the D-alanyl ester residues.

我们研究计划的主要目标是 在分子水平上理解细胞壁的生物合成。 这项研究将提供深入了解的处理 肽聚糖，青霉素作用机制，动力学 组装过程，脂质双层组织的水平， 脂磷壁酸的生物合成及其功能。 五个具体 目标将被调查。 (1)我们假设Gaffkya中PG的交联 homari发生的途径，需要青霉素敏感的N- 乙酰胞壁酰-L-丙氨酸酰胺酶和青霉素不敏感的 转肽酶 为了支持这一假设，我们的目标是分离出 从这种生物体中提取酰胺酶，并将这种酶与PBP-6联系起来， 青霉素的主要体内靶点。 (2)青霉素也会导致水溶性 PG、脂质、LTA和蛋白质。 我们的目标是建立 这些化合物的青霉素诱导释放的机制。 (3)肽聚糖形成的膜内机制是 没有很好地理解。 我们的目标是使用探针标记的脂质 中间体来研究组装过程的动力学， 脂质低聚物的形成，以及细胞膜中的膜蛋白 组装复杂。 (4)脂质双层组织在细胞膜的形成中起着重要作用。 这是我们的目标，以发展的理解， 组织，负责协会的膜 和墙，以及PG组装复杂的组织。 (5)脂磷壁酸的D-丙氨酰酯似乎起着至关重要的作用。 在细胞分裂和分离中起作用。 我们的目标是建立 D-丙氨酸掺入所需的分子事件 和D-丙氨酰酯残基的转酰作用。 这些酯在聚（甘油磷酸）上的转酰作用 部分可以代表从一个或多个分子传递信号的独特方式。 从膜的一个位置到另一个位置。 抗生素（如青霉素）对已充分表征的 装配系统有助于我们对它们的定义 行动机制。 由于新的目标网站被描述在这些 系统，提出新型抗菌剂 可以设计。 D-丙氨酰脂磷壁酸 在各种细菌粘附过程中， 传染过程 这种性质可以部分地由 D-丙氨酰酯残基。