Diverse Secreted Effectors Are Required for Salmonella Persistence in a Mouse Infection Model

Afshan S. Kidwai, Ivy Mushamiri, George S. Niemann, Roslyn N. Brown, Joshua N. Adkins, Fred Heffron

    Research output: Contribution to journalArticle

    16 Citations (Scopus)

    Abstract

    Salmonella enterica serovar Typhimurium causes typhoid-like disease in mice and is a model of typhoid fever in humans. One of the hallmarks of typhoid is persistence, the ability of the bacteria to survive in the host weeks after infection. Virulence factors called effectors facilitate this process by direct transfer to the cytoplasm of infected cells thereby subverting cellular processes. Secretion of effectors to the cell cytoplasm takes place through multiple routes, including two separate type III secretion (T3SS) apparati as well as outer membrane vesicles. The two T3SS are encoded on separate pathogenicity islands, SPI-1 and -2, with SPI-1 more strongly associated with the intestinal phase of infection, and SPI-2 with the systemic phase. Both T3SS are required for persistence, but the effectors required have not been systematically evaluated. In this study, mutations in 48 described effectors were tested for persistence. We replaced each effector with a specific DNA barcode sequence by allelic exchange and co-infected with a wild-type reference to calculate the ratio of wild-type parent to mutant at different times after infection. The competitive index (CI) was determined by quantitative PCR in which primers that correspond to the barcode were used for amplification. Mutations in all but seven effectors reduced persistence demonstrating that most effectors were required. One exception was CigR, a recently discovered effector that is widely conserved throughout enteric bacteria. Deletion of cigR increased lethality, suggesting that it may be an anti-virulence factor. The fact that almost all Salmonella effectors are required for persistence argues against redundant functions. This is different from effector repertoires in other intracellular pathogens such as Legionella.

    Original languageEnglish (US)
    Article numbere70753
    JournalPLoS One
    Volume8
    Issue number8
    DOIs
    StatePublished - Aug 12 2013

    Fingerprint

    typhoid fever
    type III secretion system
    Salmonella
    Typhoid Fever
    Virulence Factors
    Bacteria
    Genomic Islands
    DNA sequences
    mice
    Cytoplasm
    Pathogens
    virulence
    cytoplasm
    Infection
    secretion
    Legionella
    infection
    pathogenicity islands
    Amplification
    mutation

    ASJC Scopus subject areas

    • Agricultural and Biological Sciences(all)
    • Biochemistry, Genetics and Molecular Biology(all)
    • Medicine(all)

    Cite this

    Kidwai, A. S., Mushamiri, I., Niemann, G. S., Brown, R. N., Adkins, J. N., & Heffron, F. (2013). Diverse Secreted Effectors Are Required for Salmonella Persistence in a Mouse Infection Model. PLoS One, 8(8), [e70753]. https://doi.org/10.1371/journal.pone.0070753

    Diverse Secreted Effectors Are Required for Salmonella Persistence in a Mouse Infection Model. / Kidwai, Afshan S.; Mushamiri, Ivy; Niemann, George S.; Brown, Roslyn N.; Adkins, Joshua N.; Heffron, Fred.

    In: PLoS One, Vol. 8, No. 8, e70753, 12.08.2013.

    Research output: Contribution to journalArticle

    Kidwai, AS, Mushamiri, I, Niemann, GS, Brown, RN, Adkins, JN & Heffron, F 2013, 'Diverse Secreted Effectors Are Required for Salmonella Persistence in a Mouse Infection Model', PLoS One, vol. 8, no. 8, e70753. https://doi.org/10.1371/journal.pone.0070753
    Kidwai AS, Mushamiri I, Niemann GS, Brown RN, Adkins JN, Heffron F. Diverse Secreted Effectors Are Required for Salmonella Persistence in a Mouse Infection Model. PLoS One. 2013 Aug 12;8(8). e70753. https://doi.org/10.1371/journal.pone.0070753
    Kidwai, Afshan S. ; Mushamiri, Ivy ; Niemann, George S. ; Brown, Roslyn N. ; Adkins, Joshua N. ; Heffron, Fred. / Diverse Secreted Effectors Are Required for Salmonella Persistence in a Mouse Infection Model. In: PLoS One. 2013 ; Vol. 8, No. 8.
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