Staphylococcus aureus induces Gasdermin A-dependent keratinocyte pyroptosis
Doris L LaRock1, Jacob D Sherman2, Claire Qu1
1Department of Microbiology and Immunology, Emory School of Medicine, Atlanta, GA, USA.
Nature Communications
|November 26, 2025
Summary
Staphylococcus aureus triggers skin cell pyroptosis by cleaving Gasdermin A (GSDMA). This allows skin cells to eliminate the pathogen, revealing GSDMA as a direct sensor of bacterial pathogenicity.
Area of Science:
- Microbiology
- Immunology
- Cell Biology
Background:
- Staphylococcus aureus colonizes human skin and possesses high virulence.
- Distinguishing between commensal and pathogenic microbes is crucial for barrier tissues.
Purpose of the Study:
- To investigate the interaction between S. aureus and skin keratinocytes.
- To understand pathogen discrimination mechanisms in skin.
Main Methods:
- Studied the cleavage of Gasdermin A (GSDMA) by S. aureus protease Staphopain A (ScpA).
- Analyzed keratinocyte pyroptosis induced by S. aureus infection.
Main Results:
- S. aureus protease ScpA cleaves inert GSDMA in keratinocytes.
- Cleavage releases an active GSDMA fragment, inducing pyroptosis.
- Pyroptosis limits intracellular invasion of S. aureus.
Conclusions:
- GSDMA acts as an autonomous sensor of pathogenicity, unlike other gasdermins.
- This mechanism allows keratinocytes to defend against S. aureus invasion.
- Gasdermins may have broader roles in microbial threat assessment across tissues.
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