The road less traveled: transport of Legionella to the endoplasmic reticulum

Abstract

Phagosomes containing the bacterial pathogen Legionella pneumophila are transported to the ER after macrophage internalization. To modulate phagosome transport, Legionella use a specialized secretion system that injects bacterial proteins into eukaryotic cells. This review will focus on recent studies that have identified bacterial proteins and host processes that play a concerted role in transporting Legionella to the ER.

Figure 1.

Transport of a phagosome-containing Legionella to the ER. (A) Legionella resides in a plasma membrane-derived phagosome after macrophage internalization. (B) The Dot/Icm secretion system sends a signal that inhibits the fusion of endocytic organelles with the phagosome-containing Legionella. The icmS and icmW products play specific roles in this event. (C) The phagosome-containing Legionella recruits ER vesicles by a process that requires the icmR product. ER vesicles are seen attached to the phagosome-containing Legionella shortly after uptake. At this time, the RalF protein is being injected into host cells by the Dot/Icm secretion system. RalF activates the host protein ARF1, and ARF1–GTP begins to accumulate on this phagosome. (D) Legionella has established a vacuole with ER vesicles covering its surface. (E) An ER-like vacuole studded with ribosomes is created by Legionella, and it is within this organelle that bacterial replication is observed. Maintenance of this vacuole does not require continuous signaling by the Dot/Icm secretion system (Coers et al., 1999), suggesting that host factors involved in ER biogenesis are providing these functions.

Figure 2.

The Legionella-containing phagosome is converted from a vacuole surrounded by host vesicles to a replicative organelle that resembles the ER. Electron micrographs of phagosomes containing Legionella show host vesicles intimately attached to the surface of phagosomes 15 min after bacterial internalization (A). A portion of a replicative organelle identified 19 h after infection shows that the cytoplasmic surface of the vacuole membrane is at this time covered with ribosomes (B).

Figure 2.

The Legionella-containing phagosome is converted from a vacuole surrounded by host vesicles to a replicative organelle that resembles the ER. Electron micrographs of phagosomes containing Legionella show host vesicles intimately attached to the surface of phagosomes 15 min after bacterial internalization (A). A portion of a replicative organelle identified 19 h after infection shows that the cytoplasmic surface of the vacuole membrane is at this time covered with ribosomes (B).