A Legionella pneumophila effector impedes host gene silencing to promote virulence
Résumé
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.
Domaines
Sciences du Vivant [q-bio]| Origine | Fichiers produits par l'(les) auteur(s) |
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