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Legionella- and host-driven lipid flux at LCV-ER membrane contact sites promotes vacuole remodeling.
Vormittag, Simone; Hüsler, Dario; Haneburger, Ina; Kroniger, Tobias; Anand, Aby; Prantl, Manuel; Barisch, Caroline; Maaß, Sandra; Becher, Dörte; Letourneur, François; Hilbi, Hubert.
Afiliação
  • Vormittag S; Institute of Medical Microbiology, University of Zürich, Zürich, Switzerland.
  • Hüsler D; Institute of Medical Microbiology, University of Zürich, Zürich, Switzerland.
  • Haneburger I; Institute of Medical Microbiology, University of Zürich, Zürich, Switzerland.
  • Kroniger T; Institute of Microbiology, University of Greifswald, Greifswald, Germany.
  • Anand A; Division of Molecular Infection Biology and Center for Cellular Nanoanalytics, University of Osnabrück, Osnabrück, Germany.
  • Prantl M; Institute of Medical Microbiology, University of Zürich, Zürich, Switzerland.
  • Barisch C; Division of Molecular Infection Biology and Center for Cellular Nanoanalytics, University of Osnabrück, Osnabrück, Germany.
  • Maaß S; Institute of Microbiology, University of Greifswald, Greifswald, Germany.
  • Becher D; Institute of Microbiology, University of Greifswald, Greifswald, Germany.
  • Letourneur F; Laboratory of Pathogen Host Interactions, Université de Montpellier, CNRS, INSERM, Montpellier, France.
  • Hilbi H; Institute of Medical Microbiology, University of Zürich, Zürich, Switzerland.
EMBO Rep ; 24(3): e56007, 2023 03 06.
Article em En | MEDLINE | ID: mdl-36588479
Legionella pneumophila replicates in macrophages and amoeba within a unique compartment, the Legionella-containing vacuole (LCV). Hallmarks of LCV formation are the phosphoinositide lipid conversion from PtdIns(3)P to PtdIns(4)P, fusion with ER-derived vesicles and a tight association with the ER. Proteomics of purified LCVs indicate the presence of membrane contact sites (MCS) proteins possibly implicated in lipid exchange. Using dually fluorescence-labeled Dictyostelium discoideum amoeba, we reveal that VAMP-associated protein (Vap) and the PtdIns(4)P 4-phosphatase Sac1 localize to the ER, and Vap also localizes to the LCV membrane. Furthermore, Vap as well as Sac1 promote intracellular replication of L. pneumophila and LCV remodeling. Oxysterol binding proteins (OSBPs) preferentially localize to the ER (OSBP8) or the LCV membrane (OSBP11), respectively, and restrict (OSBP8) or promote (OSBP11) bacterial replication and LCV expansion. The sterol probes GFP-D4H* and filipin indicate that sterols are rapidly depleted from LCVs, while PtdIns(4)P accumulates. In addition to Sac1, the PtdIns(4)P-subverting L. pneumophila effector proteins LepB and SidC also support LCV remodeling. Taken together, the Legionella- and host cell-driven PtdIns(4)P gradient at LCV-ER MCSs promotes Vap-, OSBP- and Sac1-dependent pathogen vacuole maturation.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Legionella / Legionella pneumophila / Dictyostelium Idioma: En Revista: EMBO Rep Assunto da revista: BIOLOGIA MOLECULAR Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Suíça

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Legionella / Legionella pneumophila / Dictyostelium Idioma: En Revista: EMBO Rep Assunto da revista: BIOLOGIA MOLECULAR Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Suíça