The Salmonella-containing vacuole: moving with the times

Abstract

Salmonella pathogenesis is dependent on its ability to invade and replicate within host cells. Following invasion the bacteria remain within a modified phagosome known as the Salmonella-containing vacuole (SCV), within which they will survive and replicate. Invasion and SCV biogenesis are dependent on two Type III secretion systems, T3SS1 and T3SS2, which are used to translocate distinct cohorts of bacterial effector proteins into the host cell. Elucidating the roles of individual effector proteins in SCV biogenesis has proven difficult but several distinct themes are now emerging and it is apparent that SCV biogenesis is an extremely dynamic process involving; extensive membrane remodeling, interactions with the endolysosomal pathway, actin rearrangements and microtubule-based movement and tubule extension.

Figure 1

Schematic representation of SCV biogenesis. Salmonella invade non phagocytic cells by inducing membrane ruffles on the plasma membrane. The bacteria are internalized into the early SCV (1), which is characterized by the presence of markers of the early endocytic pathway such as EEA1 and rab5. Within 15–60 min early endosome proteins are replaced by proteins normally found on late endosome or lysosomes, such as Lamps and vATPase, and SCVs are predominantly localized near the nucleus (2). Finally after 4–6 hr bacterial replication is initiated and Sif tubules extend radially along microtubules (3). In non-polarized epithelial cells microtubules emanate from the juxtanuclear MTOC forming a radial array of uniformly polarized microtubules whose plus ends are closest to the plasma membrane. In these cells the Golgi, lysosomes and endoplasmic recycling compartment (ERC) are concentrated near the MTOC. The localization of these compartments is mediated largely by interactions with microtubule-based motors such as dynein and kinesin, which mediate retrograde (blue arrows) and anterograde movement (green arrows) respectively. Salmonella utilize the same cellular system for translocation of SCVs towards the nucleus and subsequent extension of Sifs.