Functions and Interactions of Essential PcsB in Pneumococcus Cell Wall Biosynthesis

Indiana University, Bloomington IN

Investigators

Abstract

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.