title: Subcellular targeting of Salmonella virulence proteins by host-mediated S-palmitoylation.
abstract: Several pathogenic bacteria utilize type III secretion systems (TTSS) to deliver into host cells bacterial virulence proteins with the capacity to modulate a variety of cellular pathways. Once delivered into host cells, the accurate targeting of bacterial effectors to specific locations is critical for their proper function. However, little is known about the mechanisms these virulence effectors use to reach their subcellular destination. Here we show that the Salmonella TTSS effector proteins SspH2 and SseI are localized to the plasma membrane of host cells, a process dependent on S-palmitoylation of a conserved cysteine residue within their N-terminal domains. We also show that effector protein lipidation is mediated by a specific subset of host-cell palmitoyltransferases and that lipidation is critical for effector function. This study describes a remarkable mechanism by which a pathogen exploits host-cell machinery to properly target its virulence factors.
authors.affiliation: Section of Microbial Pathogenesis, Yale University School of Medicine, New Haven, CT 06536, USA.
authors.forename: Stuart W
authors.initials: SW
authors.lastname: Hicks
authors.forename: Guillaume
authors.initials: G
authors.lastname: Charron
authors.forename: Howard C
authors.initials: HC
authors.lastname: Hang
authors.forename: Jorge E
authors.initials: JE
authors.lastname: Galán
mesh_terms: D000217:Acyltransferases / Q000235:genetics / Q000378:metabolism; D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D058947:Bacterial Secretion Systems; D002462:Cell Membrane / Q000378:metabolism; D017124:Conserved Sequence; D003545:Cysteine; D006367:HeLa Cells / Q000382:microbiology; D054884:Host-Pathogen Interactions; D006801:Humans; D054878:Lipoylation; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D011499:Protein Processing, Post-Translational; D012480:Salmonella Infections / Q000378:metabolism / Q000382:microbiology; D012486:Salmonella typhimurium / Q000378:metabolism / Q000472:pathogenicity*; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D058947:Bacterial Secretion Systems; D008565:Membrane Proteins; D037521:Virulence Factors; D000217:Acyltransferases; C549503:DHHC5 protein, mouse; D003545:Cysteine