At least four percent of the Salmonella typhimurium genome is required for fatal infection of mice

Frances Bowe, Craig J. Lipps, Renee M. Tsolis, Eduardo Groisman, Fred Heffron, Johannes G. Kusters

    Research output: Contribution to journalArticle

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    Abstract

    Salmonella typhimurium infection of mice is an established model system for studying typhoid fever in humans. Using this model, we identified S. typhimurium genes which are absolutely required to cause fatal murine infection by testing independently derived transposon insertion mutants for loss of virulence in vivo. Of the 330 mutants tested intraperitoneally and the 197 mutants tested intragastrically, 12 mutants with 50% lethal doses greater than 1,000 times that of the parental Strain were identified. These attenuated mutants were characterized by in vitro assays which correlate with known virulence functions. In addition, the corresponding transposon insertions were mapped within the S. typhimurium genome and the nucleotide sequence of the transposon-flanking DNA was obtained. Salmonella spp. and related bacteria were probed with flanking DNA for the presence of these genes. All 12 attenuated mutants had insertions in known genes, although the attenuating effects of only two of these were previously described. Furthermore, the proportion of attenuated mutants obtained in this study suggests that mutations in about 4% of the Salmonella genome lead to 1,000- fold or greater attenuation in the mouse typhoid model of infection. Most of these genes appear to be required during the early stages of a natural infection.

    Original languageEnglish (US)
    Pages (from-to)3372-3377
    Number of pages6
    JournalInfection and Immunity
    Volume66
    Issue number7
    StatePublished - Jul 1998

    Fingerprint

    Salmonella typhimurium
    Genome
    Typhoid Fever
    Infection
    Salmonella
    Genes
    Virulence
    DNA Transposable Elements
    Salmonella Infections
    Lethal Dose 50
    Bacteria
    Mutation
    DNA

    ASJC Scopus subject areas

    • Immunology

    Cite this

    Bowe, F., Lipps, C. J., Tsolis, R. M., Groisman, E., Heffron, F., & Kusters, J. G. (1998). At least four percent of the Salmonella typhimurium genome is required for fatal infection of mice. Infection and Immunity, 66(7), 3372-3377.

    At least four percent of the Salmonella typhimurium genome is required for fatal infection of mice. / Bowe, Frances; Lipps, Craig J.; Tsolis, Renee M.; Groisman, Eduardo; Heffron, Fred; Kusters, Johannes G.

    In: Infection and Immunity, Vol. 66, No. 7, 07.1998, p. 3372-3377.

    Research output: Contribution to journalArticle

    Bowe, F, Lipps, CJ, Tsolis, RM, Groisman, E, Heffron, F & Kusters, JG 1998, 'At least four percent of the Salmonella typhimurium genome is required for fatal infection of mice', Infection and Immunity, vol. 66, no. 7, pp. 3372-3377.
    Bowe F, Lipps CJ, Tsolis RM, Groisman E, Heffron F, Kusters JG. At least four percent of the Salmonella typhimurium genome is required for fatal infection of mice. Infection and Immunity. 1998 Jul;66(7):3372-3377.
    Bowe, Frances ; Lipps, Craig J. ; Tsolis, Renee M. ; Groisman, Eduardo ; Heffron, Fred ; Kusters, Johannes G. / At least four percent of the Salmonella typhimurium genome is required for fatal infection of mice. In: Infection and Immunity. 1998 ; Vol. 66, No. 7. pp. 3372-3377.
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