| Salmonella enterica serovar Typhimurium is one of the most common causes of food-borne disease world-wide. It is an invasive enteric pathogen that can successfully transit the hostile gastrointestinal environment to invade epithelial cells and establish disease in the host. In addition to gastroenteritis, infections of the elderly, neonates, and immuno-compromised individuals can result in a severe and even life-threatening disease. To fully understand how this organism causes disease, it is important to understand pathogenesis from a genomic perspective. This study has undertaken a high-throughput approach to looking at Salmonella gene expression in response to conditions that are encountered within the host environment. The construction of a random promoter library of the Salmonella genome has provided a tool to identify co-regulated genes, environment-specific responses, and explore conditions that are important for pathogenesis.; Bacteria contain many elaborately controlled networks of regulation within the cell aimed at integrating environmental signals, such as iron, for survival and adaptation. This study highlights the complexity of iron regulation, and shows that it has a prominent role in the expression of virulence-associated genes in Salmonella. By identifying a variety of iron-responsive genes, we extend our understanding of the global effect of iron availability on gene expression and virulence in the bacterial cell.; The ability of bacteria to modulate their gene expression in response to environmental changes is essential for microbes living in a competitive environment such as the gastrointestinal tract. Importantly, pathogens must be able to identify conditions specific to their host, such as iron, and respond accordingly. During the high-throughput screening, iron was shown to positively regulate the expression of invasion-associated genes, and may in fact reflect a key host condition encountered by Salmonella, in addition to bile, osmotic and oxidative stresses. Extracellular signalling may also play a role in the expression of genes in this organism.; Because of the clinical implications of this enteric pathogen, it is necessary to understand the dynamics of the host-pathogen interactions involved in Salmonella-induced gastroenteritis, including the intricacies of genetic regulation. Screens performed with the promoter library will provide a basis for defining specific conditions important in modulating gene expression in the host. These conditions will be further used to screen a S. enterica serovar Typhimurium random promoter library in an effort to identify other co-regulated promoters that may be important in Salmonella pathogenesis. |
