THE SPV GENES ON THE SALMONELLA-DUBLIN VIRULENCE PLASMID ARE REQUIREDFOR SEVERE ENTERITIS AND SYSTEMIC INFECTION IN THE NATURAL HOST

The pathogenic role of the spy (Salmonella plasmid virulence) genes of Salmonella dublin was determined in the natural, bovine host. Since t he lack of overt signs of enteritis or enterocolitis due to Salmonella infections in mice has limited the development of a convenient experi mental system to study enteric disease, we used calves to study the co ntribution of the spv genes to S. dublin-induced salmonellosis. Since the SpvR transcriptional regulator is required for expression of the s pvABCD operon, we constructed an spvR knockout mutation in a calf-viru lent strain of S. dublin, Calves were infected with the wild-type stra in, an spvR mutant, and an spvR mutant containing a complementing plas mid, Calces that were infected with the wild type or the complemented spvR mutant rapidly developed severe diarrhea and became moribund. Cal ves that were infected with the spvR mutant showed little or no clinic al signs of systemic salmonellosis and developed only mild diarrhea. T he survival and growth of the wild-type strain and the spvR mutant wer e determined by using blood-derived bovine monocytes. Wild-type S. dub lin survived and grew inside cells, while the spvR mutant did not prol iferate. These results suggest that the spv genes of S. dublin promote enhanced intracellular proliferation in intestinal tissues and at ext raintestinal sites in the natural host.