GBPs Inhibit Motility of Shigella flexneri but Are Targeted for Degradation by the Bacterial Ubiquitin Ligase IpaH9.8.
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
Research resources used in this publication
- Rabbit Anti-Ubiquitin, Lys48-Specific Monoclonal antibody, Unconjugated, Clone apu2 (RRID:AB_1587578) (antibody)
- GBP1-5 (G-12) (RRID:AB_10611378) (antibody)
- Goat Anti-Human Galectin-8 Polyclonal antibody, Unconjugated (RRID:AB_2137229) (antibody)
- GBP1 (1B1) (RRID:AB_2109333) (antibody)
- PCNA (PC10) (RRID:AB_628110) (antibody)
- Anti-Ubiquitin (linkage-specific K27) antibody [EPR17034] (RRID:AB_2713902) (antibody)
- Anti-Ubiquitin K11 linkage Antibody, clone 2A3/2E6 (RRID:AB_2713901) (antibody)
- GFP (RRID:AB_2313808) (antibody)
- Anti-Linear Ubiquitin, clone 1E3 Antibody (RRID:AB_2576212) (antibody)
- Mono- and polyubiquitinylated conjugates, mAb (FK2) (RRID:AB_10541840) (antibody)
- beta Actin antibody - Loading Control (RRID:AB_2305186) (antibody)
- Monoclonal ANTI-FLAG® M2 antibody produced in mouse (RRID:AB_262044) (antibody)
- GBP2 (G-9) (RRID:AB_10655677) (antibody)
- GBP1 antibody (RRID:AB_2247448) (antibody)
- beta Actin antibody - Loading Control (RRID:AB_2305186) (antibody)
- Monoclonal ANTI-FLAG® M2 antibody produced in mouse (RRID:AB_262044) (antibody)
- Anti-Ubiquitin (linkage-specific K27) antibody [EPR17034] (RRID:AB_2713902) (antibody)
- GBP2 (G-9) (RRID:AB_10655677) (antibody)
- GBP1-5 (G-12) (RRID:AB_10611378) (antibody)
- GBP1 (1B1) (RRID:AB_2109333) (antibody)
- GBP1 antibody (RRID:AB_2247448) (antibody)
- Goat Anti-Human Galectin-8 Polyclonal antibody, Unconjugated (RRID:AB_2137229) (antibody)
- PCNA (PC10) (RRID:AB_628110) (antibody)
- Rabbit Anti-Ubiquitin, Lys48-Specific Monoclonal antibody, Unconjugated, Clone apu2 (RRID:AB_1587578) (antibody)
- Anti-Ubiquitin K11 linkage Antibody, clone 2A3/2E6 (RRID:AB_2713901) (antibody)
- Anti-Linear Ubiquitin, clone 1E3 Antibody (RRID:AB_2576212) (antibody)
- Mono- and polyubiquitinylated conjugates, mAb (FK2) (RRID:AB_10541840) (antibody)
- GFP (RRID:AB_2313808) (antibody)
Additional research tools detected in this publication
Antibodies used in this publication
- beta Actin antibody - Loading Control (RRID:AB_2305186)
- Monoclonal ANTI-FLAG® M2 antibody produced in mouse (RRID:AB_262044)
- Anti-Ubiquitin (linkage-specific K27) antibody [EPR17034] (RRID:AB_2713902)
- GBP2 (G-9) (RRID:AB_10655677)
- GBP1-5 (G-12) (RRID:AB_10611378)
- GBP1 (1B1) (RRID:AB_2109333)
- GBP1 antibody (RRID:AB_2247448)
- Goat Anti-Human Galectin-8 Polyclonal antibody, Unconjugated (RRID:AB_2137229)
- PCNA (PC10) (RRID:AB_628110)
- Rabbit Anti-Ubiquitin, Lys48-Specific Monoclonal antibody, Unconjugated, Clone apu2 (RRID:AB_1587578)
- Anti-Ubiquitin K11 linkage Antibody, clone 2A3/2E6 (RRID:AB_2713901)
- Anti-Linear Ubiquitin, clone 1E3 Antibody (RRID:AB_2576212)
- Mono- and polyubiquitinylated conjugates, mAb (FK2) (RRID:AB_10541840)
- GFP (RRID:AB_2313808)
Associated grants
- Agency: Wellcome Trust, United Kingdom
- Agency: Medical Research Council, United Kingdom
Id: MC_U105170648 - Agency: MRF, United Kingdom
Id: MRF_MRF-104-0004-S-PATHE
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This is a list of tools and resources that we have found mentioned in this publication.
GE Healthcare (tool)
RRID:SCR_000004
A commercial antibody supplier and provider of various services.
View all literature mentionsThermo Fisher Scientific (tool)
RRID:SCR_008452
Commercial vendor and service provider of laboratory reagents and antibodies. Supplier of scientific instrumentation, reagents and consumables, and software services.
View all literature mentionsPerM (tool)
RRID:SCR_004223
THIS RESOURCE IS NO LONGER IN SERVICE. Documented on February 28,2023. Software package to perform highly efficient genome scale alignments for hundreds of millions of short reads produced by the ABI SOLiD and Illumina sequencing platforms. It capable of providing full sensitivity for alignments within 4 mismatches for 50bp SOLID reads and 9 mismatches for 100bp Illumina reads.Efficient mapping of short sequencing reads with periodic full sensitive spaced seeds.
View all literature mentionsHeLa (tool)
RRID:CVCL_0030
Cell line HeLa is a Cancer cell line with a species of origin Homo sapiens
View all literature mentionsTHP-1 (tool)
RRID:CVCL_0006
Cell line THP-1 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsbeta Actin antibody - Loading Control (antibody)
RRID:AB_2305186
This polyclonal targets RCJMB04_4h19
View all literature mentionsMonoclonal ANTI-FLAG® M2 antibody produced in mouse (antibody)
RRID:AB_262044
This monoclonal targets FLAG
View all literature mentionsAnti-Ubiquitin (linkage-specific K27) antibody [EPR17034] (antibody)
RRID:AB_2713902
This monoclonal targets Ubiquitin (linkage-specific K27)
View all literature mentionsGBP2 (G-9) (antibody)
RRID:AB_10655677
This monoclonal targets GBP2 (G-9)
View all literature mentionsGBP1-5 (G-12) (antibody)
RRID:AB_10611378
This monoclonal targets GBP1-5 (G-12)
View all literature mentionsGBP1 (1B1) (antibody)
RRID:AB_2109333
This monoclonal targets Human GBP1
View all literature mentionsGoat Anti-Human Galectin-8 Polyclonal antibody, Unconjugated (antibody)
RRID:AB_2137229
This polyclonal targets Human Galectin-8
View all literature mentionsPCNA (PC10) (antibody)
RRID:AB_628110
This monoclonal targets PCNA (PC10)
View all literature mentionsRabbit Anti-Ubiquitin, Lys48-Specific Monoclonal antibody, Unconjugated, Clone apu2 (antibody)
RRID:AB_1587578
This monoclonal targets Ubiquitin, Lys48-Specific
View all literature mentionsAnti-Ubiquitin K11 linkage Antibody, clone 2A3/2E6 (antibody)
RRID:AB_2713901
This monoclonal targets Ubiquitin K11 linkage
View all literature mentionsAnti-Linear Ubiquitin, clone 1E3 Antibody (antibody)
RRID:AB_2576212
This monoclonal targets Linear Polyubiquitin
View all literature mentionsMono- and polyubiquitinylated conjugates, mAb (FK2) (antibody)
RRID:AB_10541840
This monoclonal targets Mono- and polyubiquitinylated conjugates mAb (FK2)
View all literature mentionsRabbit Anti-Ubiquitin, Lys48-Specific Monoclonal antibody, Unconjugated, Clone apu2 (antibody)
RRID:AB_1587578
This monoclonal targets Ubiquitin, Lys48-Specific
View all literature mentionsGBP1-5 (G-12) (antibody)
RRID:AB_10611378
This monoclonal targets GBP1-5 (G-12)
View all literature mentionsGoat Anti-Human Galectin-8 Polyclonal antibody, Unconjugated (antibody)
RRID:AB_2137229
This polyclonal targets Human Galectin-8
View all literature mentionsGBP1 (1B1) (antibody)
RRID:AB_2109333
This monoclonal targets Human GBP1
View all literature mentionsPCNA (PC10) (antibody)
RRID:AB_628110
This monoclonal targets PCNA (PC10)
View all literature mentionsAnti-Ubiquitin (linkage-specific K27) antibody [EPR17034] (antibody)
RRID:AB_2713902
This monoclonal targets Ubiquitin (linkage-specific K27)
View all literature mentionsAnti-Ubiquitin K11 linkage Antibody, clone 2A3/2E6 (antibody)
RRID:AB_2713901
This monoclonal targets Ubiquitin K11 linkage
View all literature mentionsAnti-Linear Ubiquitin, clone 1E3 Antibody (antibody)
RRID:AB_2576212
This monoclonal targets Linear Polyubiquitin
View all literature mentionsMono- and polyubiquitinylated conjugates, mAb (FK2) (antibody)
RRID:AB_10541840
This monoclonal targets Mono- and polyubiquitinylated conjugates mAb (FK2)
View all literature mentionsbeta Actin antibody - Loading Control (antibody)
RRID:AB_2305186
This polyclonal targets RCJMB04_4h19
View all literature mentionsMonoclonal ANTI-FLAG® M2 antibody produced in mouse (antibody)
RRID:AB_262044
This monoclonal targets FLAG
View all literature mentionsGBP2 (G-9) (antibody)
RRID:AB_10655677
This monoclonal targets GBP2 (G-9)
View all literature mentionsbeta Actin antibody - Loading Control (antibody)
RRID:AB_2305186
This polyclonal targets RCJMB04_4h19
View all literature mentionsMonoclonal ANTI-FLAG® M2 antibody produced in mouse (antibody)
RRID:AB_262044
This monoclonal targets FLAG
View all literature mentionsAnti-Ubiquitin (linkage-specific K27) antibody [EPR17034] (antibody)
RRID:AB_2713902
This monoclonal targets Ubiquitin (linkage-specific K27)
View all literature mentionsGBP2 (G-9) (antibody)
RRID:AB_10655677
This monoclonal targets GBP2 (G-9)
View all literature mentionsGBP1-5 (G-12) (antibody)
RRID:AB_10611378
This monoclonal targets GBP1-5 (G-12)
View all literature mentionsGBP1 (1B1) (antibody)
RRID:AB_2109333
This monoclonal targets Human GBP1
View all literature mentionsGoat Anti-Human Galectin-8 Polyclonal antibody, Unconjugated (antibody)
RRID:AB_2137229
This polyclonal targets Human Galectin-8
View all literature mentionsPCNA (PC10) (antibody)
RRID:AB_628110
This monoclonal targets PCNA (PC10)
View all literature mentionsRabbit Anti-Ubiquitin, Lys48-Specific Monoclonal antibody, Unconjugated, Clone apu2 (antibody)
RRID:AB_1587578
This monoclonal targets Ubiquitin, Lys48-Specific
View all literature mentionsAnti-Ubiquitin K11 linkage Antibody, clone 2A3/2E6 (antibody)
RRID:AB_2713901
This monoclonal targets Ubiquitin K11 linkage
View all literature mentionsAnti-Linear Ubiquitin, clone 1E3 Antibody (antibody)
RRID:AB_2576212
This monoclonal targets Linear Polyubiquitin
View all literature mentionsMono- and polyubiquitinylated conjugates, mAb (FK2) (antibody)
RRID:AB_10541840
This monoclonal targets Mono- and polyubiquitinylated conjugates mAb (FK2)
View all literature mentions
