GLOBAL REGULATION OF METABOLISM AND VIRULENCE IN SALMONELLA AND DEVELOPMENT OF NOVEL VACCINES

Project: Research project

Project Details

Description

Salmonella is a facultative, intracellular pathogen responsible for disease across a broad range of hosts. Salmonella is one of the major causes of food-borne infections. Poultry and farm products (meats, eggs, fresh produce, etc.) are the major source of Salmonella infections. Following ingestion of a contaminated food or water, the organism colonizes the host's intestinal epithelium and induces gastroenteritis (i.e., salmonellosis). Salmonellosis is an important public health problem in the United States and the World. According to the Centers for Disease Control and Prevention (CDC; Atlanta GA), the number of nontyphoidal Salmonella infections in USA is ~1,400,000 cases annually. Recently, there have been many reports on contaminated peanut butter, tomatos, and poultry / meat products. Protection of the food and water supplies from Salmonella contamination is a major goal of any food safety program. There is an increasing interest in using vaccines against Salmonella serovars that are of public health concerns (i.e., S. Typhimurium and S. Enteritidis). However, most of the Salmonella strains currently in use, as live vaccines, are nutritional mutants that have a high probability of reversion. We believe that clear understanding of the virulence mechanisms and of the environmental conditions required for the expression of the virulence genes will provide better tools to combat Salmonellosis. We plan to find out how this organism copes with its changing environment during infection. We need to know the factors that are involved in the coordinated regulation of cellular metabolism, oxidative stress defenses, and pathogenesis in order to advance the development of novel strategies and therapeutics (e.g., vaccines) for the treatment and prevention of salmonellosis. We believe that coordinated regulation of cellular redox (i.e., degree of oxygenation)and steady iron concentration in S. Typhimurium is important for its ability to cause illness. These planned studies are based on our recent findings (just published in Journal of Bacteriology - 2007) that FNR (the master regulator of conditions lacking oxygen- anaerobiosis) also regulates many of the S. Typhimurium virulence genes. Furthermore, an FNR mutant was attenuated (did not cause illness), in mice. Indeed, we have a Patent application (Patent Pending) for the use of this special mutant as a live vaccine in Poultry. We also know that iron is an essential nutrient for the microbe as well as for the host, and control of iron is essential for their survival. Based on these findings and on our previous experience in microbial biology and oxidative stress, we plan to study the combined global effects of the redox and iron regulators on cellular metabolism and pathogenesis in S. Typhimurium. The results will provide novel strategies and therapeutics for the prevention of salmonellosis and possibly other diseases

StatusFinished
Effective start/end date6/1/019/30/14

Funding

  • National Science Foundation: $143,478.00

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