In this study, the Salmonella enterotoxin gene (stn) was mutated by marker
exchange mutagenesis, and the overall virulence of the organism was evaluat
ed. Salmonella marker exchange mutants evoked significantly less fluid secr
etion in mouse intestinal loops compared to that seen with wildtype S. typh
imurium. Salmonella mutants were as invasive as wild-type bacteria for HeLa
cells; however, their capacity to cause destruction of the intestinal muco
sa was impaired, when compared with wild-type bacteria by electron microsco
py. Upon oral challenge of mice, the LD50 of the Salmonella mutants was gre
ater than that for the wild-type bacteria. The fluid secretory potential, a
s well as a reduction in the LD50 of these mutants was restored when the mu
tated stn gene was replaced by the native stn gene sequence. These mutation
s had no effect on the aerobic growth of these bacteria in minimal or compl
ete medium; anaerobic growth was also not affected. With these studies, we
demonstrated that the presence of an intact stn gene contributed significan
tly to the overall virulence of S. typhimurium in a murine model. (C) 1999
Academic Press.