CHEMISTRY AND BIOSYNTHESIS OF MICROBIAL CELL WALLS

本项目的长期目标是确定 所涉及的合成酶和水解酶的特定作用 在革兰氏阴性菌胞囊和极帽的形成中， 阴性细菌;第二个广泛的目标是了解 这些酶在细胞分裂周期中的调节。 目前，这些酶中有9种被认为是敏感的 青霉素和健康相关性的研究， 细胞壁壁胞壁素和相关酶的代谢 从期望增加对这一领域的了解， 代谢将有助于青霉素的开发和正确使用 和其他β-内酰胺类抗生素。 该提案的一个具体目标是完成对 这一假说可以解释球囊的伸长 并确定青霉素敏感酶 （青霉素结合蛋白）通常参与该过程。 实验设计包括脉冲或脉冲追踪标记， 细胞与二氨基庚二酸和以下的形成和 交联肽的受体和供体半体的命运 二聚体在球囊在各种条件下， 合适的突变体，例如多突变株 构建含有A-、OPP-、一种或多种青霉素的药物， 结合蛋白突变和fts Z. 目前建议的主要方向是 长期目标是确定联合国的具体作用， 青霉素结合蛋白在小鼠构建中的作用 球囊 这需要仔细研究菌株， 或选择性抑制一种或多种青霉素结合 proteins.

The long term objective of this project is to determine the specific roles of the synthetic and hydrolytic enzymes involved in formation of the murein sacculus and the polar caps of gram negative bacteria; a second broad aim is to understand the regulation of these enzymes during the cell division cycle. Currently, 9 of these enzymes are recognized as being sensitive to penicillin and the health relatedness of a study of the metabolism of cell wall murein and the associated enzymes derives from the expectation that increased knowledge of this area of metabolism will aid in development and proper use of penicillin and other beta-lactam antibiotics. One specific aim of this proposal is to complete testing of an hypothesis which may explain how elongation of the sacculus occurs and to identify the penicillin-sensitive enzymes (penicillin-binding proteins) normally involved in the process. The experimental design involves pulse or pulse-chase labeling of cells with diamionpimelic acid and following the formation and fate of the acceptor and donor halves of the cross-linked peptide dimers in the sacculus under various conditions and in appropriate mutants such as, for example, multiple mutant strains to be constructed that contain A-, opp-, one or more penicillin- binding protein mutations, and fts Z. The main thrust of the current proposal will be directed towards the long term objective of determining the specific roles of the penicillin-binding proteins in construction of the murien sacculus. This involves careful study of strains either mutant or selectively inhibited in one or more of the penicillin-binding proteins.