FIG. 6.

L. pneumophila. L. pneumophila cells replicate within an ER-derived vacuole that avoids fusion with the default endocytic pathway. Legionella first recruits and fuses with early secretory vesicles and then subsequently interacts with the ER in an Icm/DotA-dependent manner, resulting in a ribosome-studded RV. In primary macrophages derived from bone marrow of the permissive A/J mouse, after a “pregnant pause,” the RV is delivered to lysosomes. Legionella exploits the early secretory pathway by targeting key regulators of ER-to-Golgi apparatus trafficking, including the small GTPases Rab1, Arf1, and Sar1. Rab1 is recruited to the LCV via a direct interaction with the type IV secreted effector DrrA/SidM, which functions as a Rab1-specific GEF, while LidA plays a cooperative role in recruiting and activating Rab1. Arf1 is recruited to the LCV via a direct interaction with the type IV secreted effector RalF, which functions as an Arf1 GEF. EE, early endosome; LE, late endosome; Lys, lysosome.