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A Legionella pneumophila effector impedes host gene silencing to promote virulence

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Abstract

RNA silencing is a gene silencing mechanism directed by siRNAs and miRNAs. Human miRNAs act as central regulators of host-bacteria interactions. However, it is unknown whether human pathogenic bacteria could impede RNA silencing to promote virulence. Here, we show that the Legionella pneumophila type IV-secreted effector LegK1 suppresses siRNA- and miRNA-activities in human cells. This ability depends on its kinase activity and on a functional tryptophan-dependent Argonaute (Ago)-binding platform. We further show that the capacity of LegK1 to activate NF- κ B signaling contributes to silencing suppression, demonstrating a link between effector-mediated NF- κ B signaling activation and silencing suppression. LegK1 also promotes L. pneumophila growth in both amoeba and human macrophages, supporting a key role of this effector in virulence. In infected macrophages, the latter activity relies on the genetic targeting of human Ago4, highlighting a novel function of this host factor in antibacterial resistance.
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licence : CC BY NC - Attribution - NonCommercial

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hal-03874249 , version 1 (29-11-2022)

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Attribution - NonCommercial - CC BY 4.0

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Justine Toinon, Monica Rolando, Magali Charvin, Didier Filopon, Lionel Schiavolin, et al.. A Legionella pneumophila effector impedes host gene silencing to promote virulence. 2022. ⟨hal-03874249⟩
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