The DOI matches its Crossref record; 38 of the 38 references it cites were found in a registry or an index.
Streptococcal pyrogenic exotoxin B cleaves GSDMA and triggers pyroptosis
Open accessAbstract
Gasdermins, a family of five pore-forming proteins (GSDMA–GSDME) in humans expressed predominantly in the skin, mucosa and immune sentinel cells, are key executioners of inflammatory cell death (pyroptosis), which recruits immune cells to infection sites and promotes protective immunity1,2. Pore formation is triggered by gasdermin cleavage1,2. Although the proteases that activate GSDMB, C, D and E have been identified, how GSDMA—the dominant gasdermin in the skin—is activated, remains unknown. Streptococcus pyogenes, also known as group A Streptococcus (GAS), is a major skin pathogen that causes substantial morbidity and mortality worldwide3. Here we show that the GAS cysteine protease SpeB virulence factor triggers keratinocyte pyroptosis by cleaving GSDMA after Gln246, unleashing an active N-terminal fragment that triggers pyroptosis. Gsdma1 genetic deficiency blunts mouse immune responses to GAS, resulting in uncontrolled bacterial dissemination and death. GSDMA acts as both a sensor and substrate of GAS SpeB and as an effector to trigger pyroptosis, adding a simple one-molecule mechanism for host recognition and control of virulence of a dangerous microbial pathogen. The Streptococcus pyogenes virulence factor SpeB triggers pyroptosis in keratinocytes by catalysing cleavage of host gasdermin A, a key event triggering the immune response to S. pyogenes infection.
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Citations
Cites
Neutrophil recruitment and function in health and inflammation
Kolaczkowska, E., & Kubes, P. (2013) · Nature Reviews Immunology · doi:10.1038/nri3399 · Cited by 5,472
Inflammasome-activated gasdermin D causes pyroptosis by forming membrane pores
Liu, X., Zhang, Z., Ruan, J., Pan, Y., Magupalli, V. G., Wu, H., & Lieberman, J. (2016) · Nature · doi:10.1038/nature18629 · Cited by 3,202
Self-citationPore-forming activity and structural autoinhibition of the gasdermin family
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The gasdermins, a protein family executing cell death and inflammation
Broz, P., Pelegrín, P., & Shao, F. (2020) · Nature Reviews Immunology · doi:10.1038/s41577-019-0228-2 · Cited by 1,641
GSDMD membrane pore formation constitutes the mechanism of pyroptotic cell death
Sborgi, L., Rühl, S., Mulvihill, E., Pipercevic, J., Heilig, R., Stahlberg, H., Farady, C. J., Müller, D. J., Broz, P., & Hiller, S. (2016) · The EMBO Journal · doi:10.15252/embj.201694696 · Cited by 1,152
GsdmD p30 elicited by caspase-11 during pyroptosis forms pores in membranes
Aglietti, R. A., Estevez, A., Gupta, A., Ramirez, M. G., Liu, P. S., Kayagaki, N., Ciferri, C., Dixit, V. M., & Dueber, E. C. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1607769113 · Cited by 898
Channelling inflammation: gasdermins in physiology and disease
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Self-citationQuality control, modeling, and visualization of CRISPR screens with MAGeCK-VISPR
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Self-citationStructure of the Human cGAS–DNA Complex Reveals Enhanced Control of Immune Surveillance
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Galectin-3, a marker for vacuole lysis by invasive pathogens
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Cited by
Newton, K., Strasser, A., Kayagaki, N., & Dixit, V. M. (2024) · Cell · doi:10.1016/j.cell.2023.11.044 · Cited by 990
Role of pyroptosis in inflammation and cancer
Wei, X., Xie, F., Zhou, X., Wu, Y., Yan, H., Liu, T., Huang, J., Wang, F., Zhou, F., & Zhang, L. (2022) · Cellular & Molecular Immunology · doi:10.1038/s41423-022-00905-x · Cited by 699
Pyroptosis-Induced Inflammation and Tissue Damage
Vasudevan, S. O., Behl, B., & Rathinam, V. A. (2023) · Seminars in Immunology · doi:10.1016/j.smim.2023.101781 · Cited by 412
ROS-dependent S-palmitoylation activates cleaved and intact gasdermin D
Du, G., Healy, L. B., David, L., Walker, C., El-Baba, T. J., Lutomski, C. A., Goh, B., Gu, B., Pi, X., Devant, P., et al. (2024) · Nature · doi:10.1038/s41586-024-07373-5 · Cited by 292
Self-citationMolecular mechanisms of gasdermin D pore-forming activity
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Metadata
- Authors
- Deng, W., Bai, Y., Deng, F., Pan, Y., Mei, S., Zheng, Z., Min, R., Wu, Z., Li, W., Miao, R., Zhang, Z., Kupper, T. S., Lieberman, J., & Liu, X.
- Venue
- Nature
- Published
- 2022-02-02
- Volume
- 602
- Issue
- 7897
- Pages
- 496-502
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W4210362116
- Cited by
- 348
- References
- 38
- FWCI
- 21.13
- Type
- journal article
- Language
- en
- Open access
- green
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- Deng, W., Bai, Y., Deng, F., Pan, Y., Mei, S., Zheng, Z., Min, R., Wu, Z., Li, W., Miao, R., Zhang, Z., Kupper, T. S., Lieberman, J., & Liu, X. (2022). Streptococcal pyrogenic exotoxin B cleaves GSDMA and triggers pyroptosis. Nature. https://doi.org/10.1038/s41586-021-04384-4
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