title: The Legionella effector RidL inhibits retrograde trafficking to promote intracellular replication.
abstract: The bacteria causing Legionnaires' disease, Legionella pneumophila, replicate intracellularly within unique Legionella-containing vacuoles (LCVs). LCV formation involves a type IV secretion system (T4SS) that translocates effector proteins into host cells. We show that the T4SS effector RidL localizes to LCVs, supports intracellular bacterial growth, and alters retrograde trafficking, in which selected proteins are transported from endosomes to the Golgi. The retromer complex that mediates retrograde trafficking localizes to LCVs independently of RidL and restricts intracellular bacterial growth. RidL binds the Vps29 retromer subunit and the lipid PtdIns(3)P, which localizes retromer components to membranes. Additionally, specific retromer cargo receptors and sorting nexins that mediate protein capture and membrane remodeling preferentially localize to LCVs in the absence of ridL. Ectopic RidL production inhibits retrograde trafficking, and L. pneumophila blocks retrograde transport at endosome exit sites in a ridL-dependent manner. Collectively, these findings suggest that RidL inhibits retromer function to promote intracellular bacterial replication.
authors.affiliation: Max von Pettenkofer Institute, Ludwig-Maximilians University Munich, 80336 Munich, Germany.
authors.forename: Ivo
authors.initials: I
authors.lastname: Finsel
authors.forename: Curdin
authors.initials: C
authors.lastname: Ragaz
authors.forename: Christine
authors.initials: C
authors.lastname: Hoffmann
authors.forename: Christopher F
authors.initials: CF
authors.lastname: Harrison
authors.forename: Stephen
authors.initials: S
authors.lastname: Weber
authors.forename: Vanessa A
authors.initials: VA
authors.lastname: van Rahden
authors.forename: Ludger
authors.initials: L
authors.lastname: Johannes
authors.forename: Hubert
authors.initials: H
authors.lastname: Hilbi
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D011992:Endosomes / Q000378:metabolism; D006801:Humans; D016952:Legionella pneumophila / Q000235:genetics / Q000378:metabolism*; D007877:Legionnaires' Disease / Q000378:metabolism* / Q000382:microbiology*; D051379:Mice; D021381:Protein Transport; D014617:Vacuoles / Q000378:metabolism / Q000382:microbiology*
chemical_list: D001426:Bacterial Proteins