Discovery of Salmonella virulence factors translocated via outer membrane vesicles to murine macrophages

Hyunjin Yoon, Charles Ansong, Joshua N. Adkins, Fred Heffron

    Research output: Contribution to journalArticle

    39 Citations (Scopus)

    Abstract

    Salmonella enterica serovar Typhimurium, an intracellular pathogen and leading cause of food-borne illness, encodes a plethora of virulence effectors. Salmonella virulence factors are translocated into host cells and manipulate host cellular activities, providing a more hospitable environment for bacterial proliferation. In this study, we report a new set of virulence factors that is translocated into the host cytoplasm via bacterial outer membrane vesicles (OMV). PagK (or PagK1), PagJ, and STM2585A (or PagK2) are small proteins composed of ~70 amino acids and have high sequence homology to each other (>85% identity). Salmonella lacking all three homologues was attenuated for virulence in a mouse infection model, suggesting at least partial functional redundancy among the homologues. While each homologue was translocated into the macrophage cytoplasm, their translocation was independent of all three Salmonella gene-encoded type III secretion systems (T3SSs)-Salmonella pathogenicity island 1 (SPI-1) T3SS, SPI-2 T3SS, and the flagellar system. Selected methods, including direct microscopy, demonstrated that the PagK-homologous proteins were secreted through OMV, which were enriched with lipopolysaccharide (LPS) and outer membrane proteins. Vesicles produced by intracellular bacteria also contained lysosome-associated membrane protein 1 (LAMP1), suggesting the possibility of OMV convergence with host cellular components during intracellular trafficking. This study identified novel Salmonella virulence factors secreted via OMV and demonstrated that OMV can function as a vehicle to transfer virulence determinants to the cytoplasm of the infected host cell.

    Original languageEnglish (US)
    Pages (from-to)2182-2192
    Number of pages11
    JournalInfection and Immunity
    Volume79
    Issue number6
    DOIs
    StatePublished - Jun 2011

    Fingerprint

    Virulence Factors
    Salmonella
    Macrophages
    Membranes
    Virulence
    Cytoplasm
    Lysosome-Associated Membrane Glycoproteins
    Genomic Islands
    Foodborne Diseases
    Salmonella enterica
    Sequence Homology
    Lipopolysaccharides
    Microscopy
    Membrane Proteins
    Proteins
    Bacteria
    Amino Acids
    Infection
    Genes

    ASJC Scopus subject areas

    • Immunology
    • Microbiology
    • Parasitology
    • Infectious Diseases

    Cite this

    Discovery of Salmonella virulence factors translocated via outer membrane vesicles to murine macrophages. / Yoon, Hyunjin; Ansong, Charles; Adkins, Joshua N.; Heffron, Fred.

    In: Infection and Immunity, Vol. 79, No. 6, 06.2011, p. 2182-2192.

    Research output: Contribution to journalArticle

    Yoon, Hyunjin ; Ansong, Charles ; Adkins, Joshua N. ; Heffron, Fred. / Discovery of Salmonella virulence factors translocated via outer membrane vesicles to murine macrophages. In: Infection and Immunity. 2011 ; Vol. 79, No. 6. pp. 2182-2192.
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