BIOSYNTHESIS OF BACTERIAL CELL WALLS AND MEMBRANES

细菌细胞壁和细胞膜的生物合成

• 批准号: 3124214
• 负责人: GERALD D SHOCKMAN
• 金额: $ 16.16万
• 依托单位: TEMPLE UNIV OF THE COMMONWEALTH
• 依托单位国家: 美国
• 财政年份: 1978
• 资助国家: 美国
• 起止时间: 1978-01-01 至 1987-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3124214
• 关键词: Enterococcus; antibacterial agents; autoradiography; cell cycle; cell membrane; cell wall; electron microscopy; exo alpha sialidase; membrane reconstitution /synthesis; microorganism growth; microorganism metabolism; nucleic acid inhibitor; penicillins; peptidoglycan; radiotracer; streptomycin

We will study aspects of the biosynthesis and assembly of bacterial cell surface structures - the cell wall and membrane, in relationship to cellular growth and cell division. Streptococcus faecalis ATCC 9790 (S. faecium) will be used as a "model system", primarily because of its relatively simple shape and mode of division. Future investigations will emphasize: 1. The roles of the autolytic peptidoglycan hydrolase (an N-acetylmuramidase) in cell wall growth and division. The autolytic enzyme will be isolated, purified to homogeniety and a number of its properties will be studied. Interaction of highly purified enzyme with known inhibitors of its activity such as lipoteichoic acids and phospholipids will be studied. The kinetics of synthesis, and excretion of the lipoteichoic acid inhibitor will be studied during both balanced and unbalanced growth. 2. The isolation and study of the properties of conditional mutants with defects in cell wall or membrane assembly, structure, synthesis or function. Initial emphasis will be placed on mutants with defects in their autolytic enzyme system. 3. Detailed studies of observed variations in rates of peptidoglycan synthesis and capacity to autolyze of cells in various stages of the cell division cycle. We will be particularly interested in the biochemical and molecular mechanisms for regulation of autolytic activity during normal cell division. 4. Studies of the relationship of autolytic enzyme activity to the bactericidal action of penicillins and other antibiotics that inhibit cell wall assembly. The sequence of reactions leading to cell death will be investigated as will mechanisms by which streptomycin (and other aminoglycoside antibiotics) and penicillins (and other inhibitors of cell wall assembly) act synergistically.

我们将研究细菌细胞表面的生物合成和组装 结构-细胞壁和膜，与细胞生长和 细胞分裂 粪链球菌ATCC 9790（S. 粪便）将被用作 “模式制”，主要是因为它的形态和模式比较简单， 师. 今后的研究重点是：1.自溶的作用 肽聚糖水解酶（一种N-乙酰胞壁酶）在细胞壁生长中的作用， 师. 自溶酶将被分离、纯化至均一， 将研究它的一些特性。 高纯度酶的相互作用 其活性的已知抑制剂如脂磷壁酸， 将研究磷脂。 合成和排泄的动力学 脂磷壁酸抑制剂将在平衡和非平衡期间进行研究 增长 2.条件突变体的分离及其性质的研究 细胞壁或膜组装、结构、合成或 功能 最初的重点将放在突变与缺陷，在他们的 自溶酶系统 3.详细研究了观察到的 肽聚糖的合成和细胞自溶的能力， 细胞分裂周期 我们会对生物化学特别感兴趣 正常细胞自溶活性调节的分子机制 师. 4.自溶酶活性与酶活力关系的研究 青霉素和其他抑制细胞壁的抗生素的杀菌作用 组装件. 将研究导致细胞死亡的反应顺序 链霉素（和其他氨基糖苷类抗生素） 和青霉素（以及其他细胞壁组装抑制剂） 协同地。