ArticleCell host & microbe2021
Shigella ubiquitin ligase IpaH7.8 targets gasdermin D for degradation to prevent pyroptosis and enable infection.
Article in Cell host & microbe, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 114 papers.
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114 citing papers in PubMed, 177 citations in OpenAlex.
- The gasdermin family: from pyroptosis mechanisms to therapeutic targets.Signal transduction and targeted therapy · 2026Review
- Igniting antitumour immunity with cancer cell pyroptosis.Nature reviews. Cancer · 2026Review
- Comparative insights into the apoptosome, inflammasomes and PIDDosome.Nature reviews. Immunology · 2026Review
- Targeting Gasdermins for Therapeutic Interventions in Central Nervous System Injury.Neurotoxicity research · 2026Review
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- Mechanism and plasticity of primitive pyroptosis.Science advances · 2026Article
- Cell-autonomous immunity as an integrated immune network against bacterial and viral pathogens.Nature microbiology · 2026Review
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- Ubiquitination and autophagy in host-pathogen interactions: from immune surveillance to therapeutic targeting.Nature reviews. Immunology · 2026Review
- ThebioRxiv : the preprint server for biology · 2026Article
- An overview of human inflammasomes: Activation and regulation.Journal of immunology (Baltimore, Md. : 1950) · 2026Review
- Human non-canonical inflammasomes activate CASP3 to limit intracellular Salmonella replication in macrophages.PLoS pathogens · 2026Article
- NLRP1B is an integrated decoy that subvertsProceedings of the National Academy of Sciences of the United States of America · 2026Article
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- Gasdermins against intracellular bacterial pathogens.Nature microbiology · 2026Review
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- Covalent fragment screening to inhibit the E3 ligase activity of bacterial NEL enzymes SspH1 and SspH2.RSC chemical biology · 2026Article
54 more citing papers are in PubMed but not listed here.
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19 authors at 1 institution in 1 country.
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Abstract
The pore-forming protein gasdermin D (GSDMD) executes lytic cell death called pyroptosis to eliminate the replicative niche of intracellular pathogens. Evolution favors pathogens that circumvent this host defense mechanism. Here, we show that the Shigella ubiquitin ligase IpaH7.8 functions as an inhibitor of GSDMD. Shigella is an enteroinvasive bacterium that causes hemorrhagic gastroenteritis in primates, but not rodents. IpaH7.8 contributes to species specificity by ubiquitinating human, but not mouse, GSDMD and targeting it for proteasomal degradation. Accordingly, infection of human epithelial cells with IpaH7.8-deficient Shigella flexneri results in increased GSDMD-dependent cell death compared with wild type. Consistent with pyroptosis contributing to murine disease resistance, eliminating GSDMD from NLRC4-deficient mice, which are already sensitized to oral infection with Shigella flexneri, leads to further enhanced bacterial replication and increased disease severity. This work highlights a species-specific pathogen arms race focused on maintenance of host cell viability.
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