title: Intermediate filaments enable pathogen docking to trigger type 3 effector translocation.
abstract: Type 3 secretion systems (T3SSs) of bacterial pathogens translocate bacterial effector proteins that mediate disease into the eukaryotic cytosol. Effectors traverse the plasma membrane through a translocon pore formed by T3SS proteins. In a genome-wide selection, we identified the intermediate filament vimentin as required for infection by the T3SS-dependent pathogen S. flexneri. We found that vimentin is required for efficient T3SS translocation of effectors by S. flexneri and other pathogens that use T3SS, Salmonella enterica serovar Typhimurium and Yersinia pseudotuberculosis. Vimentin and the intestinal epithelial intermediate filament keratin 18 interact with the C-terminus of the Shigella translocon pore protein IpaC. Vimentin and its interaction with IpaC are dispensable for pore formation, but are required for stable docking of S. flexneri to cells; moreover, stable docking triggers effector secretion. These findings establish that stable docking of the bacterium specifically requires intermediate filaments, is a process distinct from pore formation, and is a prerequisite for effector secretion.
authors: Division of Infectious Diseases, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.|Department of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors: Brian C
authors: BC
authors: Russo
authors: Division of Infectious Diseases, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.|Department of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors: Luisa M
authors: LM
authors: Stamm
authors: Department of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors: Matthijs
authors: M
authors: Raaben
authors: Division of Infectious Diseases, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.
authors: Caleb M
authors: CM
authors: Kim
authors: Division of Infectious Diseases, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.
authors: Emily
authors: E
authors: Kahoud
authors: Department of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors: Lindsey R
authors: LR
authors: Robinson
authors: Department of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors: Sayantan
authors: http://orcid.org/0000-0003-2397-4740
authors: S
authors: Bose
authors: Division of Infectious Diseases, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.
authors: Ana L
authors: AL
authors: Queiroz
authors: Division of Infectious Diseases, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.
authors: Bobby Brooke
authors: BB
authors: Herrera
authors: Division of Infectious Diseases, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.|Department of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors: Leigh A
authors: LA
authors: Baxt
authors: Division of Infectious Diseases, Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor, Michigan 48109, USA.
authors: Nirit
authors: N
authors: Mor-Vaknin
authors: Division of Infectious Diseases, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.
authors: Yang
authors: Y
authors: Fu
authors: Division of Infectious Diseases, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.
authors: Gabriel
authors: G
authors: Molina
authors: Division of Infectious Diseases, Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor, Michigan 48109, USA.
authors: David M
authors: DM
authors: Markovitz
authors: Department of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors: Sean P
authors: SP
authors: Whelan
authors: Division of Infectious Diseases, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.|Department of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors: Marcia B
authors: MB
authors: Goldberg
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial / Q000378:metabolism; D001422:Bacterial Adhesion; D002460:Cell Line; D054884:Host-Pathogen Interactions; D006801:Humans; D053538:Keratin-18 / Q000378:metabolism; D051379:Mice; D011485:Protein Binding; D021381:Protein Transport; D012486:Salmonella typhimurium / Q000502:physiology*; D012763:Shigella flexneri / Q000502:physiology*; D000069296:Type III Secretion Systems / Q000378:metabolism*; D014746:Vimentin / Q000378:metabolism*; D037521:Virulence Factors / Q000378:metabolism*; D015011:Yersinia pseudotuberculosis / Q000502:physiology*
chemical_list: D000942:Antigens, Bacterial; D053538:Keratin-18; D000069296:Type III Secretion Systems; D014746:Vimentin; D037521:Virulence Factors; C092342:IpaC protein, Shigella