Use of Attenuated but Metabolically Competent Salmonella as a Probiotic To Prevent or Treat Salmonella Infection
Salmonella entericais among the most burdensome of foodborne disease agents. There are over 2,600 serovars that cause a range of disease manifestations ranging from enterocolitis to typhoid fever. While there are two vaccines in use in humans to protect against typhoid fever, there are none that prevent enterocolitis. If vaccines preventing enterocolitis were to be developed, they would likely protect against only one or a few serovars. In this report, we tested the hypothesis that probiotic organisms could compete for the preferred nutrient sources ofSalmonellaand thus prevent or treat infection. To this end, we added thefralocus, which encodes a utilization pathway for theSalmonella-specific nutrient source fructose-asparagine (F-Asn), to the probiotic bacteriumEscherichia coliNissle 1917 (Nissle) to increase its ability to compete withSalmonellain mouse models. We also tested a metabolically competent, but avirulent,Salmonella entericaserovar Typhimurium mutant for its ability to compete with wild-typeSalmonella. The modified Nissle strain became more virulent and less able to protect againstSalmonellain some instances. On the other hand, the modifiedSalmonellastrain was safe and effective in preventing infection with wild-typeSalmonella. While we tested for efficacy only againstSalmonellaTyphimurium, the modifiedSalmonellastrain may be able to compete metabolically with most, if not all,Salmonellaserovars, representing a novel approach to control of this pathogen.