Figure 1.

Biogenesis of the SCV. Invasive Salmonella use T3SS1 to translocate effector proteins into host cells. Several of these effectors drive actin-mediated ruffling and internalization of the bacteria into a modified phagosome or SCV. T3SS1 effectors are also present on the SCV membrane and are important for rapid remodeling of the membranes as well as more sustained effects. The early SCV has many characteristics of early endosomes, including the phospholipid PI(3)P and proteins that interact with it such as Rab5 and SNX1. Dynamic tubular networks containing SNX1 or SNX3 are involved in membrane remodeling during this early stage in SCV biogenesis. During this initial phase of infection the majority of Salmonella down-regulate T3SS1 and induce T3SS2, which is required for subsequent steps in SCV biogenesis. The majority of SCVs relocate to a juxtanuclear location within 1–2 h and become enriched in proteins, such as Lamp1, Rab7, and vacuolar ATPase, that are normally found in late endosomes and lysosomes. However, some SCVs do not undergo this maturation process and instead either lyse and release the bacteria into the cytosol or are targeted by the autophagy system. In the mature SCV replication is initiated 4–6 h post invasion and is accompanied by the formation of a dynamic tubular network that extends from the surface of the SCV. Tubules enriched in Lamp1 are known as Sifs although another population of Lamp1-ve tubules (SISTs) has recently been described. In epithelial cells cytosolic Salmonella replicate to high numbers, compared to bacteria inside SCVs, and become re-induced for T3SS1 and flagella. Salmonella can also invade cells via T3SS1-independent mechanisms (right side), although biogenesis of the SCV under these conditions has not been well studied.