Sorting nexin-1 defines an early phase of Salmonella-containing vacuole-remodeling during Salmonella infection

Abstract

Salmonella enterica serovar Typhimurium replicate within host cells in a specialized membrane-bound compartment, the Salmonella-containing vacuole (SCV). Interaction of SCVs with the host endocytic network is modulated by bacterial effectors, some of which, such as SigD/SopB, manipulate the level of endosomal phosphoinositides. Here, we establish that at early stages of Salmonella infection, sorting nexin-1 (SNX1) - a host phosphoinositide-binding protein that normally associates with early endosomes and regulates transport to the trans-Golgi network (TGN) - undergoes a rapid and transient translocation to bacterial entry sites, an event promoted by SigD/SopB. Recruitment of SNX1 to SCVs results in the formation of extensive, long-range tubules that we have termed ;spacious vacuole-associated tubules'. Formation of these tubules is coupled with size reduction of vacuoles and the removal of TGN-resident cargo. SNX1 suppression perturbs intracellular progress of bacteria, resulting in a delayed replication. We propose that SNX1 is important in tubular-based re-modeling of nascent SCVs and, in doing so, regulates intracellular bacterial progression and replication.