Legionella pneumophila Effector RomA Uniquely Modifies Host Chromatin to Repress Gene Expression and Promote Intracellular Bacterial Replication

Abstract

Histone posttranslational modifications control eukaryotic gene expression and regulate many biological processes including immunity. Pathogens alter host epigenetic control to aid pathogenesis. We find that the intracellular bacterial pathogen Legionella pneumophila uses a Dot/Icm type IV secreted effector, RomA, to uniquely modify the host chromatin landscape. RomA, a SET domain-containing methyltransferase, trimethylates K14 of histone H3, a histone mark not previously described in mammals. RomA localizes to the infected cell nucleus where it promotes a burst of H3K14 methylation and consequently decreases H3K14 acetylation, an activating histone mark, to repress host gene expression. ChIP-seq analysis identified 4,870 H3K14 methylated promoter regions, including innate immune genes. Significantly reduced replication of a RomA-deleted strain in host cells was trans-complemented by wild-type, but not by catalytically inactive, RomA. Thus, a secreted L. pneumophila effector targets the host cell nucleus and modifies histones to repress gene expression and promote efficient intracellular replication.

Legionella pneumophila S1P-lyase targets host sphingolipid metabolism and restrains autophagy

“…To determine whether LpSpl could mimic eukaryotic SPL, we first determined its subcellular localization. Efforts to directly determine the subcellular localization of LpSpl in the host cell were unsuccessful, consistent with previous studies showing that the levels of secretion of Dot/Icm effectors are very low (31)(32)(33). However, when transfected with an Xpress-tagged form of LpSpl or a FLAG-tagged form of mSPL, both clearly localized to the ER, as has been reported for hSPL.…”

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“…Recently, a new posttranslational modification induced by L. pneumophila was reported. The Legionella-secreted effector, RomA, was shown to be a SET domain-containing methyltransferase that uniquely modifies host chromatin to repress gene expression and promote efficient intracellular bacterial replication (Rolando et al 2013). Interestingly, a combination of eukaryotic domains was predicted in several of the eukaryotic-like proteins, leading to a modular protein structure.…”