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Microbiology 147 (2001), 727-733
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Microbiology (2001), 147, 727-733.
© 2001 Society for General Microbiology


Pathogenicity and Medical Microbiology

Salmonella typhimurium thyA mutants fail to grow intracellularly in vitro and are attenuated in mice

Menno Kok1, Elisabeth Bühlmann1 and Jean-Claude Pechère1

Département de Génétique et Microbiologie, Faculté de Médecine, Université de Genève, 1 Rue Michel Servet, 1211 Genève, Switzerland1

Author for correspondence: Menno Kok. Tel: +41 22 7025652. Fax: +41 22 7025702. e-mail: menno.kok{at}medecine.unige.ch

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 P338D1 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 103 times the 50% lethal dose of the virulent parent strain.

Keywords: Salmonella, virulence, thymidylate synthase

Abbreviations: i.p., intraperitoneal; HBSS, Hanks basic salt solution; TMP, thymidine monophosphate




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[Abstract] [Full Text] [PDF]




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