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[Preprint]. 2023 Mar 20:2023.03.19.533379. [Version 1] doi: 10.1101/2023.03.19.533379

Fig. 7. Schematic model of how Legionella combats vacuole disruption in a temporally-regulated process.

Fig. 7.

Soon after internalization, the Legionella-containing vacuole is walled off with RTN4-rich tubular ER aggregates as a consequence of PR ubiquitination on RTN4 by Sde proteins (22) [Step 1. Walled off]. At early time of infection, the barrier as well as SdhA and RidL (backup vacuole guards in case the barrier is breached) protects the LCV from host membrane traffic derived from the early endosome. Over time, the wall is breached as the aggregates are dissipated by SidJ, a metaeffector that inactivates Sde proteins, (26–29) and Dups (DupA and DupB), enzymes that deubiquitinate PR-Ub-linked substrates (24, 25) [Step 2. Wall Breaks Down]. When the barrier around the LCV is dismantled, SdhA and RidL act to divert and inactivate disruptive compartments derived from the early/recycling endosomes to allow the LCV to be replication-permissive (32, 37) [Step 3. Vacuole guards].