Biomaterial Database

Streptococcal pyrogenic exotoxin B cleaves GSDMA and triggers pyroptosis. 2022

Wanyan Deng, and Yang Bai, and Fan Deng, and Youdong Pan, and Shenglin Mei, and Zengzhang Zheng, and Rui Min, and Zeyu Wu, and Wu Li, and Rui Miao, and Zhibin Zhang, and Thomas S Kupper, and Judy Lieberman, and Xing Liu

The Center for Microbes, Development and Health, Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, China.

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.

UI	MeSH Term	Description	Entries
D005098	Exotoxins	Toxins produced, especially by bacterial or fungal cells, and released into the culture medium or environment.	Exotoxin
D000069292	Pyroptosis	Type of programmed cell death associated with infection by intracellular pathogens. It is characterized by INFLAMMASOME formation; activation of CASPASE 1; and CYTOKINES mediated inflammation.	Caspase-1 Dependent Cell Death,Inflammatory Apoptosis,Pyroptotic Cell Death,Apoptoses, Inflammatory,Apoptosis, Inflammatory,Caspase 1 Dependent Cell Death,Cell Death, Pyroptotic,Cell Deaths, Pyroptotic,Death, Pyroptotic Cell,Deaths, Pyroptotic Cell,Inflammatory Apoptoses,Pyroptoses,Pyroptotic Cell Deaths
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D001426	Bacterial Proteins	Proteins found in any species of bacterium.	Bacterial Gene Products,Bacterial Gene Proteins,Gene Products, Bacterial,Bacterial Gene Product,Bacterial Gene Protein,Bacterial Protein,Gene Product, Bacterial,Gene Protein, Bacterial,Gene Proteins, Bacterial,Protein, Bacterial,Proteins, Bacterial
D013297	Streptococcus pyogenes	A species of gram-positive, coccoid bacteria isolated from skin lesions, blood, inflammatory exudates, and the upper respiratory tract of humans. It is a group A hemolytic Streptococcus that can cause SCARLET FEVER and RHEUMATIC FEVER.	Flesh-Eating Bacteria,Streptococcus Group A,Bacteria, Flesh-Eating
D051379	Mice	The common name for the genus Mus.	Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus