Salmonella pathogenicity island 2 influences both systemic salmonellosis and Salmonella-induced enteritis in calves

We have used signature-tagged mutagenesis to identify mutants of the host-s pecific Salmonella enterica serotype Dublin which were avirulent in calves and/or BALB/c mice. A mutant with a transposon insertion in the sseD gene o f Salmonella pathogenicity island 2 (SPI-2), which encodes a putative secre ted effector protein, was identified. This mutant was recovered from the bo vine host but not from the murine host following infection with a pool of s erotype Dublin mutants. However, a pure inoculum of the sseD mutant was sub sequently shown to be attenuated in calves following infection either by th e intravenous route or by the oral route. The sseD mutant was fully invasiv e for bovine intestinal mucosa but was subsequently unable to proliferate t o the same numbers as the parental strain in vivo. Both the sseD mutant and a second SPI-2 mutant, with a transposon insertion in the ssaT gene, induc ed! significantly weaker secretory and inflammatory responses in bovine lig ated ileal loops than did the parental strain. These results demonstrate th at SPI-2 is required by serotype Dublin for the induction of both systemic and enteric salmonellosis in calves.