Highly reproducible murine model of oralSalmonellainfection via inoculated food

Oral infection of mice with Salmonella Typhimurium is an important model system. In particular C57Bl/6 mice, which are susceptible to Salmonella , are used to study both systemic and gastrointestinal pathogenesis. Pretreatment with streptomycin disrupts the intestinal microbiota and results in colitis resembling human intestinal Salmonellosis . Oral gavage is typically used for delivery of both antibiotic and bacteria. Although convenient, this method requires a moderate level of expertise, can be stressful for experimental animals, and may lead to unwanted tracheal or systemic introduction of bacteria. Here, we demonstrate a simple method for oral infection of mice using small pieces of regular mouse chow inoculated with a known number of bacteria. Mice readily ate chow pieces containing up to 10 8 CFU Salmonella , allowing for a wide range of infectious doses. In mice pretreated with streptomycin, infection with inoculated chow resulted in less variability in numbers of bacteria recovered from tissues compared to oral gavage, and highly consistent infections even at doses as low as 10 3 Salmonella . Mice not treated with streptomycin, as well as resistant Nramp1 reconstituted C57Bl/6J mice, were also readily infected using this method. In summary, we show that foodborne infection of mice by feeding with pieces of chow inoculated with Salmonella results in infection comparable to oral gavage but represents a natural route of infection with fewer side effects and less variability among mice.