The Enteropathogenic E. coli Effector EspF Targets and Disrupts the Nucleolus by a Process Regulated by Mitochondrial Dysfunction

Paul Dean, Jon Scott, Andrew Knox, Sabine Quitard, Nicholas Watkins, Brendan Kenny, Guy Tran Van Nhieu (Editor)

    Research output: Contribution to journalArticle

    Abstract

    The nucleolus is a multifunctional structure within the nucleus of eukaryotic cells and is the primary site of ribosome biogenesis. Almost all viruses target and disrupt the nucleolus—a feature exclusive to this pathogen group. Here, using a combination of bio-imaging, genetic and biochemical analyses, we demonstrate that the enteropathogenic E. coli (EPEC) effector protein EspF specifically targets the nucleolus and disrupts a subset of nucleolar factors. Driven by a defined N-terminal nucleolar targeting domain, EspF causes the complete loss from the nucleolus of nucleolin, the most abundant nucleolar protein. We also show that other bacterial species disrupt the nucleolus, dependent on their ability to deliver effector proteins into the host cell. Moreover, we uncover a novel regulatory mechanism whereby nucleolar targeting by EspF is strictly controlled by EPEC's manipulation of host mitochondria. Collectively, this work reveals that the nucleolus may be a common feature of bacterial pathogenesis and demonstrates that a bacterial pathogen has evolved a highly sophisticated mechanism to enable spatio-temporal control over its virulence proteins
    Original languageEnglish
    Pages (from-to)e1000961
    JournalPLoS Pathogens
    Volume6
    Issue number6
    DOIs
    Publication statusPublished - 2010

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