BIOSYNTHESIS OF BACTERIAL CELL WALLS AND MEMBRANES

细菌细胞壁和细胞膜的生物合成

• 批准号: 3124216
• 负责人: GERALD D SHOCKMAN
• 金额: $ 17.27万
• 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 1988-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3124216
• 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方面 结构 - 细胞壁和膜与细胞生长和 细胞分裂。 粪便果球菌ATCC 9790（S.粪便）将用作A “模型系统”，主要是因为其相对简单的形状和模式 分配。 未来的调查将强调：1。自溶作用 细胞壁生长和 分配。 自溶酶将被分离，纯化为均质，A 将研究其属性的数量。 高纯化酶的相互作用 具有其活性的已知抑制剂，例如脂肪酸和 将研究磷脂。 合成的动力学和排泄 在平衡和不平衡期间，将研究脂肪乙酸抑制剂 生长。 2。隔离和研究条件突变体的性质 在细胞壁或膜组件，结构，合成或 功能。 最初的重点将放在具有缺陷的突变体上 自溶酶系统。 3。关于观察到的速率变化的详细研究 肽聚糖的合成和在各个阶段自动化细胞的能力 细胞分裂周期。 我们将对生化特别感兴趣 正常细胞期间自溶活性调节的分子机制 分配。 4.自溶酶活性与 青霉素和其他抑制细胞壁的杀菌作用 集会。 将研究导致细胞死亡的反应序列 链霉素（和其他氨基糖苷抗生素）的机制也是如此 和青霉素（以及细胞壁组装的其他抑制剂）ACT 协同。