CHEMISTRY AND BIOSYNTHESIS OF MICROBIAL CELL WALLS

该项目的长期目标是确定 合成酶和水解酶的特殊作用 在毛尿囊和革兰氏极帽的形成中 阴性细菌；第二个广泛的目标是了解 在细胞分裂周期中对这些酶的调节。 目前，这些酶中有9种被认为是敏感的 青霉素与健康相关性的一项研究 细胞壁粘蛋白及其相关酶的代谢 由于预期对这一领域的了解增加， 新陈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。 这项提议的一个具体目标是完成对 这一假说可以解释球囊的伸长 并对青霉素敏感酶进行鉴定 (青霉素结合蛋白)通常参与这一过程。 实验设计包括脉冲或脉冲追逐标记 细胞中含有二氨基戊二酸，并在形成和 交联肽的受体和供体的命运 球囊中的二聚体在各种条件下和在 适当的突变体，例如多个突变菌株 被构造为含有A-、Opp-、一种或多种青霉素- 结合蛋白突变和FTS Z。 目前提案的主旨将指向 确定委员会的具体作用的长期目标 青霉素结合蛋白在菌落构建中的作用 球囊。这涉及到对突变株或突变株的仔细研究 或选择性地抑制青霉素结合中的一种或多种 蛋白质。

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.