Legionella Metaeffector Exploits Host Proteasome to Temporally Regulate Cognate Effector

• DOI: 10.1371/journal.ppat.1001216
• Publication Date: 2010-12-02T20:55:51Z
• Authors: Tomoko Kubori; Naoaki Shinzawa; Hirotaka Kanuka; Hiroki Nagai
• Keywords: 0301 basic medicine; Proteasome Endopeptidase Complex; Time Factors; QH301-705.5; Ubiquitin-Protein Ligases; Legionella; RC581-607; Cell Line; Legionella pneumophila; 03 medical and health sciences; Drosophila melanogaster; Bacterial Proteins; Host-Pathogen Interactions; Animals; Immunologic diseases. Allergy; Biology (General); Research Article

Pathogen-associated secretion systems translocate numerous effector proteins into eukaryotic host cells to coordinate cellular processes important for infection. Spatiotemporal regulation is therefore important for modulating distinct activities of effectors at different stages of infection. Here we provide the first evidence of "metaeffector," a designation for an effector protein that regulates the function of another effector within the host cell. Legionella LubX protein functions as an E3 ubiquitin ligase that hijacks the host proteasome to specifically target the bacterial effector protein SidH for degradation. Delayed delivery of LubX to the host cytoplasm leads to the shutdown of SidH within the host cells at later stages of infection. This demonstrates a sophisticated level of coevolution between eukaryotic cells and L. pneumophila involving an effector that functions as a key regulator to temporally coordinate the function of a cognate effector protein.