The Salmonella effector SteA binds phosphatidylinositol 4-phosphate for subcellular targeting within host cells

Lia Domingues, Ahmad Ismail, Nuno Charro, Isabel Rodríguez-Escudero, David W. Holden, María Molina, Víctor J. Cid, Luís Jaime Mota

Research output: Contribution to journalArticlepeer-review

24 Citations (Scopus)

Abstract

Many bacterial pathogens use specialized secretion systems to deliver virulence effector proteins into eukaryotic host cells. The function of these effectors depends on their localization within infected cells, but the mechanisms determining subcellular targeting of each effector are mostly elusive. Here, we show that the Salmonella type III secretion effector SteA binds specifically to phosphatidylinositol 4-phosphate [PI(4)P]. Ectopically expressed SteA localized at the plasma membrane (PM) of eukaryotic cells. However, SteA was displaced from the PM of Saccharomyces cerevisiae in mutants unable to synthesize the local pool of PI(4)P and from the PM of HeLa cells after localized depletion of PI(4)P. Moreover, in infected cells, bacterially translocated or ectopically expressed SteA localized at the membrane of the Salmonella-containing vacuole (SCV) and to Salmonella-induced tubules; using the PI(4)P-binding domain of the Legionella type IV secretion effector SidC as probe, we found PI(4)P at the SCV membrane and associated tubules throughout Salmonella infection of HeLa cells. Both binding of SteA to PI(4)P and the subcellular localization of ectopically expressed or bacterially translocated SteA were dependent on a lysine residue near the N-terminus of the protein. Overall, this indicates that binding of SteA to PI(4)P is necessary for its localization within host cells.

Original languageEnglish
Pages (from-to)949-969
Number of pages21
JournalCellular Microbiology
Volume18
Issue number7
DOIs
Publication statusPublished - 1 Jul 2016

Keywords

  • PATHOGENICITY ISLAND 2
  • III SECRETION SYSTEM
  • ENTERICA SEROVAR TYPHIMURIUM
  • INTRACELLULAR REPLICATION
  • BACTERIAL EFFECTORS
  • CONTAINING VACUOLE
  • MEMBRANE DYNAMICS
  • VIRULENCE PROTEIN
  • EPITHELIAL-CELLS
  • YEAST

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