Transcriptional Regulation of a major virulence operon in Staphylococcus aureus: Insights from biochemcial genomic and proteomic studies

点击翻译按钮获取中文摘要

Staphylococcus aureus is a bacterium that is often referred to as a 'superbug' because of its ability to cause a diverse range of human and animal diseases and to resist antibiotic treatment (e.g. the MRSA-strain). S. aureus is a major human and animal pathogen because it can produce a wide range of virulence factors, which allow the bacterium to attach itself to the host, evade the host immune system and to rapidly degrade host tissue through the production of potent toxins, e.g. haemolysins which break down blood cells. The expression of genes in S. aureus responsible for the production of virulence factors are tightly controlled by several gene regulatory systems. It is generally accepted that the so called 'agr system' is the 'master' regulatory system involved in the control and expression of virulence genes in S. aureus. Here, we propose to study how the expression of the 'agr system' itself is controlled in the different stages of growth of S. aureus cells and in response to the environmental conditions encountered by S. aureus cells during growth and infection. In particular, we will describe and indentify the component interactions between proteins and DNA that contribute to 'switching on' the agr system. This study will provide one of the fewest examples, where a major virulence-linked gene regulatory system is described at the molecular level in a clinically significant bacterial pathogen. Thus, the outcome of this research will generate valuable resources and a knowledge base for the academic and clinical research communities and those in industrial settings seeking to exploit the agr system to create novel drugs for the treatment of staphylococcal infections.