Salmonella typhimurium disseminates within its host by manipulating the motility of infected cells

Micah J. Worley, George S. Nieman, Kaoru Geddes, Fred Heffron

    Research output: Contribution to journalArticle

    87 Citations (Scopus)

    Abstract

    The mammalian host has a number of innate immune mechanisms designed to limit the spread of infection, yet many bacteria, including Salmonella, can cause systemic disease. Salmonella typhimurium-infected phagocytes traverse the gastrointestinal (GI) epithelium and enter the bloodstream within minutes after ingestion, thereby spreading throughout its host. Here, we provide a cellular and molecular basis for this phenomenon. We demonstrate that S. typhimurium manipulates the migratory properties of infected GI phagocytes with a type III secretion system. We show that one secreted effector, SrfH, interacts with the host protein TRIP6, a member of the zyxin family of adaptor proteins that regulate motility. SrfH promotes phagocyte motility in vitro and accelerates the systemic spread of infection away from the lumen of the intestine in the mouse. This is a previously uncharacterized mechanism by which an intracellular pathogen overcomes host defenses designed to immobilize infected cells.

    Original languageEnglish (US)
    Pages (from-to)17915-17920
    Number of pages6
    JournalProceedings of the National Academy of Sciences of the United States of America
    Volume103
    Issue number47
    DOIs
    StatePublished - Nov 21 2006

    Fingerprint

    Salmonella typhimurium
    Phagocytes
    Cell Movement
    Zyxin
    Molecular Motor Proteins
    Infection
    Salmonella
    Intestines
    Epithelium
    Eating
    Bacteria
    Proteins

    Keywords

    • Bacteremia
    • Secreted effector
    • TRIP6
    • Type 3 secretion
    • Virulence

    ASJC Scopus subject areas

    • Genetics
    • General

    Cite this

    Salmonella typhimurium disseminates within its host by manipulating the motility of infected cells. / Worley, Micah J.; Nieman, George S.; Geddes, Kaoru; Heffron, Fred.

    In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 103, No. 47, 21.11.2006, p. 17915-17920.

    Research output: Contribution to journalArticle

    Worley, Micah J. ; Nieman, George S. ; Geddes, Kaoru ; Heffron, Fred. / Salmonella typhimurium disseminates within its host by manipulating the motility of infected cells. In: Proceedings of the National Academy of Sciences of the United States of America. 2006 ; Vol. 103, No. 47. pp. 17915-17920.
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    abstract = "The mammalian host has a number of innate immune mechanisms designed to limit the spread of infection, yet many bacteria, including Salmonella, can cause systemic disease. Salmonella typhimurium-infected phagocytes traverse the gastrointestinal (GI) epithelium and enter the bloodstream within minutes after ingestion, thereby spreading throughout its host. Here, we provide a cellular and molecular basis for this phenomenon. We demonstrate that S. typhimurium manipulates the migratory properties of infected GI phagocytes with a type III secretion system. We show that one secreted effector, SrfH, interacts with the host protein TRIP6, a member of the zyxin family of adaptor proteins that regulate motility. SrfH promotes phagocyte motility in vitro and accelerates the systemic spread of infection away from the lumen of the intestine in the mouse. This is a previously uncharacterized mechanism by which an intracellular pathogen overcomes host defenses designed to immobilize infected cells.",
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