The Salmonella Biochemistry of Inflammation

Salmonella-induced gastroenteritis is the single most common cause of death from food-borne infectious illness in the United Sates (US). S. enterica serotype Typhimurium (S. Typhimurium) is associated most frequently with this diarrheal disease. S. Typhimurium causes acute intestinal inflammation by invading the intestinal epithelium and surviving within macrophages in the mucosa. <P> Current research on S. Typhimurium pathogenesis is beginning to paint a novel picture of the unique challenges and opportunities encountered during life in the inflamed intestine. New insights into the consequences inflammation has on the growth conditions encountered by microbes residing in the intestinal lumen raise the question which properties enable S. Typhimurium to thrive in this environment. <P> The long term-goal of the proposed research is to identify mechanisms that allow S. Typhimurium to prosper in the lumen of the inflamed intestine, thereby promoting transmission by the fecal-oral route. Our central hypothesis is that inflammation enables S. Typhimurium to catabolize 1 2 propanediol, a fermentation product of fucose, to CO2 using tetrathionate respiration, thereby gaining an advantage during growth in the inflamed gut. <P> We will test different aspects of our hypothesis by pursuing the following specific aims: 1. Determine the role of fucose utilization during growth in the lumen of the inflamed gut. 2. Determine the role of tetrathionate respiration for gaining a luminal growth advantage during inflammation. This application is highly innovative, since the proposed experiments will for the first time explore the unique biochemistry of intestinal inflammation. <P> Public Health Relevance: Non-typhoidal Salmonella serotypes are the single most common cause of death from diarrheal disease associated with viruses, parasites or bacteria and the leading cause of food borne disease outbreaks in the United States, producing between $0.5 billion to $2.3 billion in annual costs for medical care and lost productivity. The most common human clinical isolates are Salmonella enterica serotypes Typhimurium (S. Typhimurium) and Enteritidis (S. Enteritidis). <P> Research proposed in this application will support the pioneering studies needed to understand how S. Typhimurium uses intestinal inflammation to outgrow other bacteria in the intestine, a key property for the remarkable epidemiological success of this enteric pathogen.