Contribution ofSalmonella typhimuriumVirulence Factors to Diarrheal Disease in Calves

Abstract
Limited knowledge is available about the virulence mechanisms responsible for diarrheal disease caused bySalmonella typhimurium. To assess the contribution to diarrheal disease of virulence determinants identified in models of infection, we tested a collection ofS. typhimuriummutants for their ability to cause enteritis in calves.S. typhimuriumstrains carrying mutations in the virulence plasmid (spvR),Salmonellapathogenicity island 2 (SPI-2) (spiB), or SPI-5 (sopB) caused mortality and acute diarrhea in calves. AnS. typhimurium rfaJmutant, which is defective for lipopolysaccharide outer core biosynthesis, was of intermediate virulence. Mutations in SPI-1 (hilAandprgH) oraroAmarkedly reduced virulence and the severity of diarrhea. Furthermore, histopathological examination of calves infected with SPI-1 oraroAmutants revealed a marked reduction or absence of intestinal lesions. These data suggest that virulence factors, such as SPI-1, which are required during intestinal colonization are more important for pathogenicity in calves than are genes required during the systemic phase ofS. typhimuriuminfection, including SPI-2 or thespvoperon. This is in contrast to the degree of attenuation caused by these mutations in the mouse.