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Record W4416721843 · doi:10.1038/s41467-025-65674-3

Staphylococcus aureus induces Gasdermin A-dependent keratinocyte pyroptosis

2025· article· en· W4416721843 on OpenAlexafffund
Doris L. LaRock, Jacob D. Sherman, Chen Qu, William Shu Ching Ngai, Timothy D. Read, Martin J. McGavin, Christopher N. LaRock

Bibliographic record

VenueNature Communications · 2025
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicInflammasome and immune disorders
Canadian institutionsWestern University
FundersNational Center for Advancing Translational SciencesNational Institute of Allergy and Infectious DiseasesCanadian Institutes of Health ResearchSchool of Medicine, Emory UniversityU.S. Department of Health and Human ServicesGovernment of CanadaNational Institutes of HealthEmory UniversityBurroughs Wellcome Fund
KeywordsPyroptosisStaphylococcus aureusVirulenceProteasePseudomonas aeruginosaIntracellularPathogenKeratinocyteProteases

Abstract

fetched live from OpenAlex

Staphylococcus aureus is a common colonizer of human skin, which, despite its ubiquitous nature, has a high virulence potential. Tolerating microbes in health but responding effectively to pathogens presents a challenge to the barrier tissues. Here, we examined the interaction of S. aureus with skin keratinocytes to study this early step of pathogenesis and pathogen discrimination. During infection, the S. aureus protease Staphopain A (ScpA) cleaves inert Gasdermin A (GSDMA). This releases an active N-terminal fragment similar to that formed by host protease regulators of other gasdermins family members. The resulting cell death by pyroptosis allows keratinocytes to deprive invasive S. aureus of an intracellular niche. These data support a model of GSDMA as an autonomous sensor of pathogenicity, in contrast to the conventional regulation of other gasdermins, which have dedicated host cell pathways. Gasdermins abundant in other tissues may have similar functions in host defense for the threat assessment of a microbe. The cell death effector Gasdermin A is only known to be activated by Streptococcus pyogenes. This work discovers a mechanism for its activation by Staphylococcus aureus, and shows a conserved role in immunity against invasive skin pathogens

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.001
Threshold uncertainty score0.004

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0010.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.009
GPT teacher head0.288
Teacher spread0.279 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations4
Published2025
Admission routes2
Has abstractyes

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