The enteropathogenic E. coli effector EspF targets and disrupts the nucleolus by a process regulated by mitochondrial dysfunction.
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.
Dean
Paul
P
Institute for Cell and Molecular Biosciences, Medical School, University of Newcastle, Newcastle upon Tyne, United Kingdom. p.dean@ncl.ac.uk
Scott
Jon A
JA
Knox
Andrew A
AA
Quitard
Sabine
S
Watkins
Nicholas J
NJ
Kenny
Brendan
B
D000595:Amino Acid Sequence; D015153:Blotting, Western; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002466:Cell Nucleolus / Q000502:physiology*; D004269:DNA, Bacterial / Q000235:genetics; D054308:Enteropathogenic Escherichia coli / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*; D004927:Escherichia coli Infections / Q000378:metabolism / Q000382:microbiology / Q000473:pathology*; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D006367:HeLa Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008928:Mitochondria / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology*; D008969:Molecular Sequence Data; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D016133:Polymerase Chain Reaction; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D000097796:Nucleolin
D002352:Carrier Proteins; D004269:DNA, Bacterial; D029968:Escherichia coli Proteins; D047908:Intracellular Signaling Peptides and Proteins; D010750:Phosphoproteins; D016601:RNA-Binding Proteins; D000097796:Nucleolin; C489109:EspFU protein, E coli