A galE via (Vi antigen-negative) mutant of Salmonella typhi Ty2 retains virulence in humans.
We have recently described the construction of a galE derivative of Salmonella typhi Ty2 (Ty2H1) which had a 0.4-kilobase deletion in the galE gene and was sensitive to galactose-induced lysis when cultured with greater than or equal to 0.06 mM galactose (D. M. Hone, R. Morona, S. Attridge, and J. Hackett, J. Infect. Dis. 156:167-174, 1987). We now report the selection of a rifampin-resistant, via derivative of Ty2H1, EX462. Compared with the Ty2 parent strain, EX462 was serum sensitive and highly attenuated in the mouse mucin virulence assay. When four human volunteers ingested 7 X 10(8) viable EX462, two became ill and developed a typhoidlike disease with fever and bacteremia. Blood isolates from these individuals were indistinguishable from the vaccine strain by a variety of criteria. We concluded that, even in a via background, the galE mutation was not attenuating for S. typhi in humans.
Hone
D M
DM
Department of Microbiology and Immunology, University of Adelaide, South Australia.
Attridge
S R
SR
Forrest
B
B
Morona
R
R
Daniels
D
D
LaBrooy
J T
JT
Bartholomeusz
R C
RC
Shearman
D J
DJ
Hackett
J
J
D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis; D000942:Antigens, Bacterial / Q000235:genetics / Q000276:immunology*; D001428:Bacterial Vaccines / Q000276:immunology*; D001770:Blood Bactericidal Activity; D004195:Disease Models, Animal; D005690:Galactose / Q000378:metabolism; D005798:Genes, Bacterial; D006801:Humans; D066298:In Vitro Techniques; D008070:Lipopolysaccharides / Q000378:metabolism; D051379:Mice; D009154:Mutation; D012485:Salmonella typhi / Q000235:genetics / Q000472:pathogenicity*; D013045:Species Specificity
D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001428:Bacterial Vaccines; D008070:Lipopolysaccharides; D005690:Galactose