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
Externally publishedYes

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, 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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