We have developed a novel ileal loop model for use in calves to analyze the contribution of Salmonella enterica serovar Typhimurium
type III secretion systems to disease processes in vivo. Our model involves constructing ileal loops with end-to-end anastamoses to restore the patency of the small intestine, thereby allowing experimental animals to convalesce following surgery for the desired number of days. This model overcomes the time constraint imposed by ligated ileal loop models that have precluded investigation of Salmonella
virulence factors during later stages of the
infection process. Here, we have used this model to examine the enteric disease process at 24 h and 5 days following
infection with wild-type Salmonella and mutants lacking the virulence-associated Salmonella pathogenicity island 1 (SPI-1) or SPI-2
type III secretion systems. We show that SPI-2 mutants are dramatically attenuated at 5 days following
infection and report a new phenotype for
SPI-1 mutants, which induce intestinal pathology in calves similar to wild-type Salmonella in the 5-day ileal loop model. Both of these temporal phenotypes for
SPI-1 and SPI-2 mutants were corroborated in a second animal model of enteric disease using
streptomycin-pretreated mice. These data delineate novel phenotypes for
SPI-1 and SPI-2 mutants in the intestinal phase of bovine and murine
salmonellosis and provide working models to further investigate the effector contribution to these pathologies.