Construction and characterization of vaccine strains of Salmonella harboring mutations in two different aro genes.
Derivatives of the mouse-virulent Salmonella typhimurium strain SL1344 were constructed harboring stable mutations in aroC alone or in aroC and aroA together. Fifty percent lethal doses after intravenous inoculation of the mutants into BALB/c mice were determined, and the mutants were as highly attenuated as were SL1344 aroA derivatives. All aro-dependent derivatives persisted in vivo at similar levels and for similar intervals in the livers and spleens of BALB/c mice infected intravenously. Mice vaccinated orally with 10(10) live organisms of the different derivatives survived and were well protected against oral challenge with virulent S. typhimurium. A Salmonella typhi Ty2 derivative, designated WBL2000, was constructed that harbors well-defined, stable mutations in both aroA and aroC.
Dougan
G
G
Department of Molecular Biology, Wellcome Research Laboratories, Beckenham, Kent, England.
Chatfield
S
S
Pickard
D
D
Bester
J
J
O'Callaghan
D
D
Maskell
D
D
D051229:3-Phosphoshikimate 1-Carboxyvinyltransferase; D019883:Alkyl and Aryl Transferases; D000818:Animals; D001428:Bacterial Vaccines; D015139:Blotting, Southern; D005798:Genes, Bacterial; D008190:Lyases / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D009154:Mutation; D019761:Phosphorus-Oxygen Lyases; D012485:Salmonella typhi / Q000201:enzymology / Q000235:genetics* / Q000276:immunology; D012486:Salmonella typhimurium / Q000201:enzymology / Q000235:genetics* / Q000276:immunology; D013753:Tetracycline Resistance; D014161:Transduction, Genetic; D014166:Transferases / Q000235:genetics*; D014613:Vaccines, Attenuated; D014614:Vaccines, Synthetic
D001428:Bacterial Vaccines; D014613:Vaccines, Attenuated; D014614:Vaccines, Synthetic; D014166:Transferases; D019883:Alkyl and Aryl Transferases; D051229:3-Phosphoshikimate 1-Carboxyvinyltransferase; D008190:Lyases; C019895:chorismate synthase; D019761:Phosphorus-Oxygen Lyases