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DNA Adenine Methylase Mutants of S. typhimurium as Modified Live Vaccines in Calves


Salmonella is the most commonly isolated infectious enteric bacterial pathogen of dairy cattle and the most common disease associated with human consumption of beef and dairy products. In recent years there has been a rise in the incidence and severity of human cases of salmonellosis, in part due to the emergence of the antimicrobial resistant S. typhimurium in cattle populations. On large commercial dairy farms it is very common for cattle to be exposed to many Salmonella strains and for calves to become infected shortly after birth. Under these conditions it would be desirable to have a Salmonella vaccine capable of stimulating immunity to many Salmonella strains. The overall goal of this proposal is to test the hypothesis that S. typhimurium lacking the DNA adenine methylase (Dam) are effective live vaccines against Salmonella infection of cattle.

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This proposal is based on our recent discovery that S. typhimurium containing mutations in the Dam gene are totally avirulent yet confer full protection against murine typhoid fever when used as live vaccines. We propose to determine whether Dam-derivatives of Salmonella are attenuated for virulence in calves and whether they can serve as live vaccines that elicit immunity to many Salmonella strains.The proposed vaccines will have a profound influence on reducing salmonellosis in cattle and on improving the safety of beef and dairy products. Moreover, these vaccines may have utility in other livestock species, which would provide a means of controlling Salmonella in livestock production systems and enhancing the safety of the food supply.

Mahan, Michael
University of California - Santa Barbara
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