Structural Studies on the Intracellular Steps that Govern the Staphylococcus aureus Quorum Sensing System.

Abstract

Quorum sensing in bacteria has been extensively examined over the past two decades. These studies suggest that the molecular mechanism that governs quorum sensing incorporates niche-specific, environmentally sensitive information in addition to chemosensory information embedded in the signaling molecules- autoinducing peptides (AIPs) or homoserine lactones. One aspect of the quorum sensing mechanism that was examined in the course of this study was the sensitivity and fidelity of the intracellular signal transduction cascade that correlates extracellular information with a cellular response. The Agr quorum-sensing system in Staphylococcus aureus provided a good model system to examine this aspect of the mechanism. As individual components of this mechanism had been characterized by other groups earlier, the tools to probe the intracellular cascade existed at the start of this project. This thesis describes the progress made in the course of studies to examine the role of two important intracellular components- AgrC and AgrA. These proteins were examined using a variety of biophysical, biochemical and structural biology techniques.