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 journalArticleResearchpeer-review

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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Enteropathogenic Escherichia coli
Escherichia coli Proteins
Eukaryotic Cells
Nuclear Proteins
Ribosomes
Virulence
Molecular Biology
Mitochondria
Proteins
Viruses
nucleolin

Cite this

Dean, Paul ; Scott, Jon ; Knox, Andrew ; Quitard, Sabine ; Watkins, Nicholas ; Kenny, Brendan ; Van Nhieu, Guy Tran (Editor). / The Enteropathogenic E. coli Effector EspF Targets and Disrupts the Nucleolus by a Process Regulated by Mitochondrial Dysfunction. In: PLoS Pathogens. 2010 ; Vol. 6, No. 6. pp. e1000961.
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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",
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The Enteropathogenic E. coli Effector EspF Targets and Disrupts the Nucleolus by a Process Regulated by Mitochondrial Dysfunction. / Dean, Paul; Scott, Jon ; Knox, Andrew; Quitard, Sabine; Watkins, Nicholas ; Kenny, Brendan; Van Nhieu, Guy Tran (Editor).

In: PLoS Pathogens, Vol. 6, No. 6, 2010, p. e1000961.

Research output: Contribution to journalArticleResearchpeer-review

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