ALegionella pneumophilaeffector impedes host gene silencing to promote virulence

Abstract

AbstractRNA 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 theLegionella pneumophilatype 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-κB signaling contributes to silencing suppression, demonstrating a link between effector-mediated NF-κB signaling activation and silencing suppression. LegK1 also promotesL. pneumophilagrowth 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.