Legionella pneumophila SidD is a deAMPylase that modifies Rab1

A pathogen's protein armoury Legionella pneumophila secretes multiple effectors into host cells during infection, some of which modify host trafficking and thereby aid intracellular replication. One of these modifications is AMPylation of Rab1 by L. pneumophila SidM. This study adds another layer to this regulation by demonstrating that a second L. pneumophila effector, SidD, deAMPylates Rab1. The identification of SidD suggests that this pathogen uses a specific set of proteins to hijack the activity of Rab1 for its own purposes. Legionella pneumophila actively modulates host vesicle trafficking pathways to facilitate its intracellular replication with effectors translocated by the Dot/Icm type IV secretion system (T4SS) 1 . The SidM/DrrA protein functions by locking the small GTPase Rab1 into an active form by its guanine nucleotide exchange factor (GEF) and AMPylation activity 2 , 3 , 4 . Here we demonstrate that the L. pneumophila protein SidD preferably deAMPylates Rab1. We found that the deAMPylation activity of SidD could suppress the toxicity of SidM to yeast and is required to release Rab1 from bacterial phagosomes efficiently. A molecular mechanism for the temporal control of Rab1 activity in different phases of L. pneumophila infection is thus established. These observations indicate that AMPylation-mediated signal transduction is a reversible process regulated by specific enzymes.