Dynein-mediated Vesicle Transport Controls IntracellularSalmonellaReplication

Abstract

Salmonella typhimurium survives and replicates intracellular in a membrane-bound compartment, the Salmonella-containing vacuole (SCV). In HeLa cells, the SCV matures through interactions with the endocytic pathway, but Salmonella avoids fusion with mature lysosomes. The exact mechanism of the inhibition of phagolysosomal fusion is not understood. Rab GTPases control several proteins involved in membrane fusion and vesicular transport. The small GTPase Rab7 regulates the transport of and fusion between late endosomes and lysosomes and associates with the SCV. We show that the Rab7 GTPase cycle is not affected on the SCV. We then manipulated a pathway downstream of the small GTPase Rab7 in HeLa cells infected with Salmonella. Expression of the Rab7 effector RILP induces recruitment of the dynein/dynactin motor complex to the SCV. Subsequently, SCV fuse with lysosomes. As a result, the intracellular replication of Salmonella is inhibited. Activation of dynein-mediated vesicle transport can thus control intracellular survival of Salmonella.

The Salmonella effector protein PipB2 is a linker for kinesin-1

“…Perhaps SifA regulates some low level of kinesin-1 recruited to the SCV independent of PipB2 or possesses another unidentified activity, the lack of which is responsible for SCV membrane instability and the atypical intracellular positioning. This activity could possibly be the regulation of another molecular motor such as dynein because inhibition of dynein activity has been shown to stabilize the sifA Ϫ SCV to the same extent as does inhibition of kinesin activity (18), and this retrograde molecular motor is recruited onto the SCV by binding to a rab7͞RILP complex under certain circumstances (24,25). SifA contains a pentapeptide motif that has the potential to mimic small GTPases in their active GTP-bound form (26) and thus could potentially modulate the rab7͞RILP͞dynein cascade (27).…”

The Salmonella-containing vacuole—Moving with the times

“…But other data suggests that SpiC is a component of the T3SS2 translocon rather than an effector [39] and this issue remains unresolved. Redistribution of SCVs from the cell periphery to the MTOC/juxtanuclear region is mediated at least in part by the small GTP-binding protein rab7 together with its effector RILP, which are required for recruitment of the microtubule-based motor dynein [40][41][42]. Once at the MTOC two T3SS2 effectors that have the ability to interact with one another, SseG and SseF, are required to maintain SCV positioning over longer periods of time [43][44][45].…”

B Cell Receptor-Mediated Internalization of Salmonella: A Novel Pathway for Autonomous B Cell Activation and Antibody Production

“…typhimurium SL1344 (Salmonella) (25), GFP-Salmonella (26), and mRFPSalmonella (27) were described before. GFP-Salmonella defective in SPI-1 (invA mutant) or SPI-2 (ssrA mutant) were a gift from M. Rescigno (European Institute of Oncology, Milan, Italy).…”