Functions and Interactions of Essential PcsB in Pneumococcus Cell Wall Biosynthesis

本项目的目标是确定的定位，生化功能，和相互作用的基本，细胞外PcsB蛋白，这在胞壁素生物合成中起着重要作用，并介导的革兰氏阳性细菌肺炎链球菌（肺炎球菌）的细胞形状。将实现三个相关的具体目标。艾姆岛PcsB蛋白的定位将通过免疫荧光显微术确定。此外，表型的pcsB突变体，可能表明功能和相互作用的特点。Aim II.将表征PcsB的生化功能，包括与其他表面蛋白和肽聚糖组分的相互作用。Aim III.无偏遗传方法将用于获得更多的信息PcsB功能和相互作用。智力上的优点。本研究将为革兰氏阳性菌肽聚糖生物合成和结构的几个基本过程提供新的信息和见解。它将提供有关关键PcsB蛋白的新数据，该蛋白在其他物种中是保守的。此外，它将提供令人兴奋的新信息之间的联系胞壁合成和细胞形状决定球形细菌。更广泛的影响。该项目对培训、科学基础设施以及可能对社会产生广泛影响。该项目将有助于培养本科生和研究生。它将应用和改进遗传方法用于模式生物S。肺炎。最后，这笔赠款将导致PcsB的验证，表征和检测开发，这有可能成为抗生素开发的新目标。

The goal of this project is to determine the localization, biochemical functions, and interactions of the essential, extracellular PcsB protein, which plays an important role in murein biosynthesis and mediates the cell shape of the gram positive bacterium Streptococcus pneumoniae (pneumococcus). Three related Specific Aims will be accomplished. Aim I. The localization of the PcsB protein will be determined by immunofluorescent microscopy. In addition, phenotypes of pcsB mutants that might indicate functions and interactions will be characterized. Aim II. The biochemical function(s) of PcsB will be characterized, including interactions with other surface proteins and peptidoglycan components. Aim III. Unbiased genetic approaches will be used to gain more information about PcsB functions and interactions. Intellectual merit. This research will provide new information and insights about several fundamental processes in peptidoglycan biosynthesis and architecture in gram positive bacteria. It will provide new data about the critical PcsB protein, which is conserved in other species of streptococcus. In addition, it will provide exciting new information about the links between murein biosynthesis and cell shape determination in spherically shaped bacteria. Broader Impact. This project has broad impact to training, scientific infrastructure, and possibly to society. The project will contribute to the training of undergraduate and graduate students. It will apply and refine genetic methods for use in the model organism,S. pneumoniae. Finally, this grant will lead to the validation, characterization, and assay development of PcsB, which has the potential to become a new target for antibiotic development.