Abstract
The intracellular bacterial pathogen Legionella pneumophila targets conserved eukaryotic pathways to establish a replicative niche inside host cells. With a host range that spans billions of years of evolution (from protists to humans), the interaction between L. pneumophila and its hosts frequently involves conserved eukaryotic pathways (protein translation, ubiquitination, membrane trafficking, autophagy, and the cytoskeleton). Here, we present the identification of a new, highly conserved host target of L. pneumophila effectors: the CCR4-NOT complex. CCR4-NOT modulates mRNA stability in eukaryotes from yeast to humans, making it an attractive target for a generalist pathogen, such as L. pneumophila. We show that the uncharacterized L. pneumophila effector PieF specifically targets one component of this complex, the deadenylase subunit CNOT7/8. We show that the interaction between PieF and CNOT7 is direct, occurs with high affinity, and reshapes the catalytic activity, localization, and composition of the complex across evolutionarily diverse eukaryotic cells.
Published Version
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