Contribution of Salmonella typhimurium virulence factors to diarrheal disease in calves

Limited knowledge is available about the virulence mechanisms responsible f or diarrheal disease caused by Salmonella typhimurium. To assess the contri bution to diarrheal disease of virulence determinants identified in models of infection, we tested a collection of S. typhimurium mutants for their ab ility to cause enteritis in calves. S. typhimurium strains carrying mutatio ns in the virulence plasmid (spvR), Salmonella pathogenicity island 2 (SPI- 2) (spiB), or SPI-5 (sopB) caused mortality and acute diarrhea in calves. A n S. typhimurium rfaJ mutant, which is defective for lipopolysaccharide out er core biosynthesis, was of intermediate virulence. Mutations in SPI-1 (hi lA and prgH) or aroA markedly reduced virulence and the severity of diarrhe a. Furthermore, histopathological examination of calves infected with SPI-1 or aroA mutants revealed a marked reduction or absence of intestinal lesio ns. These data suggest that virulence factors, such as SPI-1, which are req uired during intestinal colonization are more important for pathogenicity i n calves than are genes required during the systemic phase of S. typhimuriu m infection, including SPI-2 or the spy operon. This is in contrast to the degree of attenuation caused by these mutations in the mouse.