Salmonella entericaserotype Typhimurium requires a functional type III secretion system encoded bySalmonellapathogenicity island 1 (SPI1) to cause diarrhea. We investigated the role of genes encoding secreted target proteins of the SPI1-associated type III secretion system for enteropathogenicity in calves.Salmonellaserotype Typhimurium strains having mutations insptP,avrA,sspH1, orslrPinduced fluid secretion in the bovine ligated ileal loop model at levels similar to that of the wild type. In contrast, mutations insipA,sopA,sopB,sopD, orsopE2significantly reduced fluid accumulation in bovine ligated ileal loops at 8 h postinfection. A strain carrying mutations insipA,sopA,sopB,sopD, andsopE2(sipA sopABDE2mutant) caused the same level of fluid accumulation in bovine ligated ileal loops as a strain carrying a mutation insipB, a SPI1 gene required for the translocation of effector proteins into host cells. A positive correlation was observed between the severity of histopathological lesions detected in the ileal mucosa and the levels of fluid accumulation induced by the different mutants. After oral infection of calves, theSalmonellaserotype TyphimuriumsipAsopABDE2mutant caused only mild diarrhea and was more strongly attenuated than strains having only single mutations. These data demonstrate that SipA, SopA, SopB, SopD, and SopE2 are major virulence factors responsible for diarrhea duringSalmonellaserotype Typhimurium infection of calves.

Recent studies on the molecular pathogenesis of Salmonella enterica serotype Typhimurium-induced enterocolitis using tissue culture models and the neonatal calf model have led to an improved understanding of key events occurring during the complex series of host-pathogen interactions leading to