Intermediate filaments enable pathogen docking to trigger type 3 effector translocation

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 filam...

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Bibliographic Details
Published in:	Nature microbiology Vol. 1; no. 4; p. 16025
Main Authors:	Russo, Brian C., Stamm, Luisa M., Raaben, Matthijs, Kim, Caleb M., Kahoud, Emily, Robinson, Lindsey R., Bose, Sayantan, Queiroz, Ana L., Herrera, Bobby Brooke, Baxt, Leigh A., Mor-Vaknin, Nirit, Fu, Yang, Molina, Gabriel, Markovitz, David M., Whelan, Sean P., Goldberg, Marcia B.
Format:	Journal Article
Language:	English
Published:	London Nature Publishing Group UK 07-03-2016 Nature Publishing Group
Subjects:	14/34 14/63 45/70 631/326/41/2180 631/326/421 631/326/88 631/80/128/1580 82/111 Animals Antigens, Bacterial - metabolism Bacterial Adhesion Biomedical and Life Sciences C-Terminus Cell Line Cytosol Filaments Genomes Host-Pathogen Interactions Humans Infectious Diseases Intermediate filaments Intestine Keratin Keratin-18 - metabolism Life Sciences Medical Microbiology Mice Microbiology Parasitology Pathogens Protein Binding Protein Transport Pseudotuberculosis Salmonella typhimurium - physiology Secretion Shigella flexneri - physiology Type III Secretion Systems - metabolism Vimentin Vimentin - metabolism Virology Virulence Factors - metabolism Yersinia pseudotuberculosis - physiology
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Summary:	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. Binding of type 3 secretion system translocons to host intermediate filaments mediate Shigella , Salmonella and Yersinia docking and facilitate effector translocation.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Current Affiliations: Liver Diseases Therapeutic Area, Gilead Sciences, Foster City, CA 94404, USA Current Affiliations: Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA Current Affiliations: Netherlands Cancer Institute, 1066 CX, Amsterdam, NL Current Affiliations: Center for Computational and Integrative Biology, Massachusetts General Hospital, Boston, MA 02114, USA
ISSN:	2058-5276 2058-5276
DOI:	10.1038/nmicrobiol.2016.25