The COPII complex and lysosomal VAMP7 determine intracellular Salmonella localization and growth

Salmonella invades epithelial cells and survives within a membrane-bound compartment, the Salmonella-containing vacuole (SCV). We isolated and determined the host protein composition of the SCV at 30 min and 3 h of infection to identify and characterize novel regulators of intracellular bacterial localization and growth. Quantitation of the SCV protein content revealed 392 host proteins specifically enriched at SCVs, out of which 173 associated exclusively with early SCVs, 124 with maturing SCV and 95 proteins during both time-points. Vacuole interactions with endoplasmic reticulum-derived coat protein complex II vesicles modulate early steps of SCV maturation, promoting SCV rupture and bacterial hyper-replication within the host cytosol. On the other hand, SCV interactions with VAMP7-positive lysosome-like vesicles promote Salmonella-induced filament formation and bacterial growth within the late SCV. Our results reveal that the dynamic communication between the SCV and distinct host organelles affects both intracellular Salmonella localization and growth at successive steps of host cell invasion.