Virotrap Reveals Salmonella SopB as A Ubiquitinated Cargo for Host ESCRT-0

The pathogenic bacterium Salmonella survives and replicates in host cells within a Salmonella-containing vacuole (SCV), a membranous niche it actively remodels via secreted effectors. The phosphoinositide phosphatase SopB is a key effector implicated in SCV biogenesis, yet its host protein interactome has remained incompletely defined. Using the mass spectrometry-based interactomics technology Virotrap, we identify a novel set of SopB-associated host proteins, including the ESCRT-0 subunit HGS and other membrane remodeling proteins. We demonstrate that SopB directly interacts with HGS via its ubiquitin-binding domains, and show that SopB promotes ESCRT-0 recruitment to the SCV, yet ultimately counteracts its anti-replicative effect. As the ESCRT machinery plays a central role in cargo sorting and membrane remodeling, we propose a new SopB-dependent strategy by which Salmonella hijacks host endosomal trafficking to build its intracellular niche.