Salmonella SirA is a global regulator of genes mediating enteropathogenesis

Brian M M Ahmer, Jeroen Van Reeuwijk, Patricia R. Watson, Tim S. Wallis, Fred Heffron

    Research output: Contribution to journalArticle

    151 Citations (Scopus)

    Abstract

    SirA of Salmonella typhimurium is known to regulate the hilA and prgH genes within Salmonella pathogenicity island 1 (SPI1). To identify more members of the SirA regulon, we screened 10,000 random lacZY fusions (chromosomal MudJ insertions) for regulation by SirA and identified 10 positively regulated fusions. Three fusions were within the SPI1 genes hilA (an SPI1 transcriptional regulator), spaS (a component of the SPI1 type III export apparatus) and sipS (a substrate of the SPI1 export apparatus). Two fusions were within the sopB gene (also known as sigD). sopB is located within SPI5, but encodes a protein that is exported via the SPI1 export apparatus. In addition, five fusions were within genes of unknown function that are located in SPI4. As spaS and sipB were likely to be hilA dependent, we tested all of the fusions (except hilA) for hilA dependence. Surprisingly, we found that all of the fusions require hilA for expression and that plasmid-encoded SirA cannot bypass this requirement. Therefore, SirA regulates hilA, the product of which regulates genes within SPI1, SPI4 and SPI5. Both sirA and hilA mutants are dramatically attenuated in a bovine model of gastroenteritis, but have little or no effect in the mouse model of typhoid fever. This study establishes the SirA/HilA regulatory cascade as the primary regulon controlling enteropathogenic virulence functions in S. typhimurium. Because S. typhimurium causes gastroenteritis in both cattle and humans, we believe that this information may be directly applicable to the human disease.

    Original languageEnglish (US)
    Pages (from-to)971-982
    Number of pages12
    JournalMolecular Microbiology
    Volume31
    Issue number3
    DOIs
    StatePublished - 1999

    Fingerprint

    Genomic Islands
    Regulator Genes
    Salmonella
    Salmonella typhimurium
    Regulon
    Genes
    Gastroenteritis
    Typhoid Fever
    Virulence
    Plasmids

    ASJC Scopus subject areas

    • Molecular Biology
    • Microbiology

    Cite this

    Ahmer, B. M. M., Van Reeuwijk, J., Watson, P. R., Wallis, T. S., & Heffron, F. (1999). Salmonella SirA is a global regulator of genes mediating enteropathogenesis. Molecular Microbiology, 31(3), 971-982. https://doi.org/10.1046/j.1365-2958.1999.01244.x

    Salmonella SirA is a global regulator of genes mediating enteropathogenesis. / Ahmer, Brian M M; Van Reeuwijk, Jeroen; Watson, Patricia R.; Wallis, Tim S.; Heffron, Fred.

    In: Molecular Microbiology, Vol. 31, No. 3, 1999, p. 971-982.

    Research output: Contribution to journalArticle

    Ahmer, BMM, Van Reeuwijk, J, Watson, PR, Wallis, TS & Heffron, F 1999, 'Salmonella SirA is a global regulator of genes mediating enteropathogenesis', Molecular Microbiology, vol. 31, no. 3, pp. 971-982. https://doi.org/10.1046/j.1365-2958.1999.01244.x
    Ahmer, Brian M M ; Van Reeuwijk, Jeroen ; Watson, Patricia R. ; Wallis, Tim S. ; Heffron, Fred. / Salmonella SirA is a global regulator of genes mediating enteropathogenesis. In: Molecular Microbiology. 1999 ; Vol. 31, No. 3. pp. 971-982.
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