Salmonella typhimurium thyA mutants fail to grow intracellularly in vitro and are attenuated in mice.
Salmonella typhimurium ATCC14028 readily multiplies in professional phagocytes in vitro and is highly virulent in mice. Mutants lacking thymidylate synthase activity (thyA) were isolated and shown to be strictly dependent on thymidine monophosphate precursors in the growth medium. The thyA mutants were found to be virtually incapable of intracellular growth and survival in vitro, both in macrophage-like cell line P338D(1) and in the human epithelial cell line Hep-2, and their virulence was impaired in BALB/c mice. Intraperitoneal immunization of mice with two doses of live S. typhimurium thyA provided protection against a challenge with 10(3) times the 50% lethal dose of the virulent parent strain.
Kok
Menno
M
Département de Génétique et Microbiologie, Faculté de Médecine, Université de Genève, 1 Rue Michel Servet, 1211 Genève, Switzerland1.
Bühlmann
Elisabeth
E
Département de Génétique et Microbiologie, Faculté de Médecine, Université de Genève, 1 Rue Michel Servet, 1211 Genève, Switzerland1.
Pechère
Jean-Claude
JC
Département de Génétique et Microbiologie, Faculté de Médecine, Université de Genève, 1 Rue Michel Servet, 1211 Genève, Switzerland1.
D000818:Animals; D002460:Cell Line; D006801:Humans; D008264:Macrophages / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D009154:Mutation; D012480:Salmonella Infections / Q000382:microbiology*; D012486:Salmonella typhimurium / Q000201:enzymology / Q000235:genetics / Q000254:growth & development* / Q000472:pathogenicity*; D013940:Thymidylate Synthase / Q000235:genetics* / Q000378:metabolism; D014774:Virulence
D013940:Thymidylate Synthase