BIOSYNTHESIS OF BACTERIAL CELL WALL COMPONENTS

细菌细胞壁成分的生物合成

• 批准号: 3124194
• 负责人: FRANCIS C NEUHAUS
• 金额: $ 18.5万
• 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 1992-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3124194
• 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; 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 从分子水平上理解细胞壁的生物合成。 这项研究将为我们深入了解 肽聚糖(PG)，青霉素作用机制，动力学 组装过程、脂质双层组织的水平，以及 脂磷壁酸的生物合成和功能。五个具体 将对AIMS进行调查。 (1)我们的假设是在Gaffkya中PG的交联 Homari通过一条需要青霉素敏感的N- 乙酰胞外酰胺L丙氨酸酰胺酶与青霉素不敏感菌株 转肽酶。为了支持这一假设，我们的目标是将 这种有机体中的酰胺酶，并将其与PBP-6联系起来， 青霉素的主要体内靶点。 (2)青霉素还可引起水溶蛋白分泌增加。 PG、脂质、LTA和蛋白质。我们的目标是建立 青霉素诱导这些化合物释放的机制。 (3)肽聚糖形成的膜内机制为 不是很清楚。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， 脂质低聚体的形成，以及细胞内的膜蛋白 装配综合体。 (4)脂质双层结构在细胞周期中起着重要作用。 PG装配。我们的目标是加深对 负责膜协会的组织 和墙，以及PG组装综合体的组织。 (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的作用。我们的目标是建立 D-丙氨酸掺入所需的分子事件 和D-丙氨酰基酯残基的转酰化。 这些酯在聚甘油磷酸酯上的转酰化反应 部分可以表示将信号从 从膜上的一个位置到另一个位置。 抗生素，如青霉素，对具有良好特性的 装配系统对我们定义它们的 行动机制。随着新目标站点在这些站点中的描述 系统，提出了新型抗菌剂 可能是专门设计的。D-丙氨酰脂磷壁酸已被牵连 在各种细菌黏附过程中参与的 传染过程。这一属性可以部分地由 D-丙氨酸乙酯残留物。