Intermediate filaments enable pathogen docking to trigger type 3 effector translocation.
Brian C RussoLuisa M StammMatthijs RaabenCaleb M KimEmily KahoudLindsey R RobinsonSayantan BoseAna L QueirozBobby Brooke HerreraLeigh A BaxtNirit Mor-VakninYang FuGabriel MolinaDavid M MarkovitzSean P WhelanMarcia B GoldbergPublished in: Nature microbiology (2016)
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.
Keyphrases
- protein protein
- type iii
- molecular dynamics
- molecular dynamics simulations
- regulatory t cells
- dendritic cells
- small molecule
- genome wide
- induced apoptosis
- gram negative
- dna methylation
- candida albicans
- cell cycle arrest
- antimicrobial resistance
- gene expression
- immune response
- oxidative stress
- endoplasmic reticulum stress
- binding protein
- pi k akt