title: 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.
authors.affiliation: Henry Wellcome Integrated Signalling Laboratories, Department of Biochemistry, School of Medical Sciences, University of Bristol, Bristol, UK.
authors.forename: Miriam V
authors.initials: MV
authors.lastname: Bujny
authors.forename: Phil A
authors.initials: PA
authors.lastname: Ewels
authors.forename: Suzanne
authors.initials: S
authors.lastname: Humphrey
authors.forename: Naomi
authors.initials: N
authors.lastname: Attar
authors.forename: Mark A
authors.initials: MA
authors.lastname: Jepson
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Cullen
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D015415:Biomarkers; D004269:DNA, Bacterial / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D021381:Protein Transport; D034741:RNA, Small Interfering; D012480:Salmonella Infections / Q000378:metabolism* / Q000382:microbiology; D012486:Salmonella typhimurium / Q000378:metabolism*; D017384:Sequence Deletion; D058305:Sorting Nexins; D014162:Transfection; D014617:Vacuoles / Q000201:enzymology / Q000235:genetics; D033921:Vesicular Transport Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D021601:trans-Golgi Network / Q000201:enzymology / Q000235:genetics
chemical_list: D001426:Bacterial Proteins; D015415:Biomarkers; D004269:DNA, Bacterial; D034741:RNA, Small Interfering; C513978:SNX1 protein, human; D058305:Sorting Nexins; D033921:Vesicular Transport Proteins; C489224:SopB protein, Salmonella