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Interferon exposure boosts cell-autonomous immunity for more efficient pathogen control. But how interferon-enhanced immunity protects the cytosol against bacteria and how professionally cytosol-dwelling bacteria avoid clearance are insufficiently understood. Here we demonstrate that the interferon-induced GTPase family of guanylate-binding proteins (GBPs) coats Shigella flexneri in a hierarchical manner reliant on GBP1. GBPs inhibit actin-dependent motility and cell-to-cell spread of bacteria but are antagonized by IpaH9.8, a bacterial ubiquitin ligase secreted into the host cytosol. IpaH9.8 ubiquitylates GBP1, GBP2, and GBP4 to cause the proteasome-dependent destruction of existing GBP coats. This ubiquitin coating of Shigella favors the pathogen as it liberates bacteria from GBP encapsulation to resume actin-mediated motility and cell-to-cell spread. We conclude that an important function of GBP recruitment to S. flexneri is to prevent the spread of infection to neighboring cells while IpaH9.8 helps bacterial propagation by counteracting GBP-dependent cell-autonomous immunity.
Pubmed ID: 29024643 RIS Download
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View all literature mentionsCell line HeLa is a Cancer cell line with a species of origin Homo sapiens
View all literature mentionsCell line THP-1 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsThis polyclonal targets RCJMB04_4h19
View all literature mentionsThis monoclonal targets FLAG
View all literature mentionsThis monoclonal targets Ubiquitin (linkage-specific K27)
View all literature mentionsThis monoclonal targets GBP2 (G-9)
View all literature mentionsThis monoclonal targets GBP1-5 (G-12)
View all literature mentionsThis monoclonal targets Human GBP1
View all literature mentionsThis polyclonal targets Human Galectin-8
View all literature mentionsThis monoclonal targets PCNA (PC10)
View all literature mentionsThis monoclonal targets Ubiquitin, Lys48-Specific
View all literature mentionsThis monoclonal targets Ubiquitin K11 linkage
View all literature mentionsThis monoclonal targets Linear Polyubiquitin
View all literature mentionsThis monoclonal targets Mono- and polyubiquitinylated conjugates mAb (FK2)
View all literature mentionsThis monoclonal targets Ubiquitin, Lys48-Specific
View all literature mentionsThis monoclonal targets GBP1-5 (G-12)
View all literature mentionsThis polyclonal targets Human Galectin-8
View all literature mentionsThis monoclonal targets Human GBP1
View all literature mentionsThis monoclonal targets PCNA (PC10)
View all literature mentionsThis monoclonal targets Ubiquitin (linkage-specific K27)
View all literature mentionsThis monoclonal targets Ubiquitin K11 linkage
View all literature mentionsThis monoclonal targets Linear Polyubiquitin
View all literature mentionsThis monoclonal targets Mono- and polyubiquitinylated conjugates mAb (FK2)
View all literature mentionsThis polyclonal targets RCJMB04_4h19
View all literature mentionsThis monoclonal targets FLAG
View all literature mentionsThis monoclonal targets GBP2 (G-9)
View all literature mentionsThis polyclonal targets RCJMB04_4h19
View all literature mentionsThis monoclonal targets FLAG
View all literature mentionsThis monoclonal targets Ubiquitin (linkage-specific K27)
View all literature mentionsThis monoclonal targets GBP2 (G-9)
View all literature mentionsThis monoclonal targets GBP1-5 (G-12)
View all literature mentionsThis monoclonal targets Human GBP1
View all literature mentionsThis polyclonal targets Human Galectin-8
View all literature mentionsThis monoclonal targets PCNA (PC10)
View all literature mentionsThis monoclonal targets Ubiquitin, Lys48-Specific
View all literature mentionsThis monoclonal targets Ubiquitin K11 linkage
View all literature mentionsThis monoclonal targets Linear Polyubiquitin
View all literature mentionsThis monoclonal targets Mono- and polyubiquitinylated conjugates mAb (FK2)
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