One bacterial effector with two distinct catalytic activities by different strains

Abstract

The causative agent of Legionnaires' disease, Legionella pneumophila , is a master manipulator of various eukaryotic hosts ranging from unicellular amoebae to mammals [1]. This intracellular pathogen, which invades macrophages in mammalian hosts, evades the default endosome–lysosome pathway and remodels the phagosome, enclosing it in an endoplasmic reticulum‐derived Legionella ‐containing vacuole (LCV). L. pneumophila facilitates this by hijacking a myriad of eukaryotic cellular functions through translocation of around 300 effectors into the host cell by the Dot/Icm type IVB secretion apparatus. More than 70 of the injected effector proteins contain eukaryotic‐like domains, including the ankyrin repeat, Sel1, F‐box, SET, U‐box and leucine‐rich repeats, which suggests L. pneumophila hijacks and manipulates various eukaryotic processes through molecular mimicry. Elegant work by Rolando et al [2] and Li et al [3] described a new effector, designated RomA or LegAS4, respectively, which exhibits molecular mimicry of host SET‐domain‐containing histone methyltransferases to hijack host transcriptional programming by methylating histones on specific lysine residues [2,3]. Histone methylation has a crucial role in epigenetic control of gene transcription. Prior to these findings, no intracellular pathogen had been shown to directly affect chromatin architecture to alter the host cell transcriptional landscape. Rolando and Li both show that RomA/LegAS4 is a histone methyltransferase, but that the functional phenotype of RomA/LegAS4 is different in the two strains of L. pneumophila used in the two studies. Rolando et al primarily used the …