Abstract
The bacterium Legionella pneumophila secretes numerous effector proteins that manipulate endoplasmic reticulum (ER)-derived vesicles to form the Legionella-containing vacuole (LCV). Despite extensive studies, whether the LCV membrane is separate from or connected to the host ER network remains unclear. Here, we show that the smooth ER (sER) is closely associated with the LCV early in infection. Remarkably, Legionella forms a distinct rough ER (rER) niche at later stages, disconnected from the host ER network. We discover that host small GTPases Rab10 and Rab4 and an ER protein, BAP31, play crucial roles in transitioning the LCV from an sER to an rER. Additionally, we have identified a Legionella effector, Lpg1152, that binds to BAP31. Interestingly, the optimal growth of Legionella is dependent on both BAP31 and Lpg1152. These findings detail the complex interplay between host and pathogen in transforming the LCV membrane from a host-associated sER to a distinct rER.