MétaCan
Menu
Back to cohort
Record W3165053782 · doi:10.1111/cmi.13371

Candidalysin triggers epithelial cellular stresses that induce necrotic death

2021· article· en· W3165053782 on OpenAlexafffund
Mariana Blagojevic, Giorgio Camilli, Michelle E. Maxson, Bernhard Hube, David L. Moyes, Jonathan P. Richardson, Julian R. Naglik

Bibliographic record

VenueCellular Microbiology · 2021
Typearticle
Languageen
FieldMedicine
TopicAntifungal resistance and susceptibility
Canadian institutionsHospital for Sick Children
FundersNational Institute of Dental and Craniofacial ResearchBiotechnology and Biological Sciences Research CouncilCanadian Institutes of Health ResearchDirectorate for Biological SciencesKing's College LondonDeutsche ForschungsgemeinschaftWellcome TrustNational Institutes of HealthPfizer
KeywordsBiologyProgrammed cell deathCandida albicansApoptosisCell biologySecretionNecrosisCellMitochondrionCell damageMicrobiologyBiochemistry

Abstract

fetched live from OpenAlex

Candida albicans is a common opportunistic fungal pathogen that causes a wide range of infections from superficial mucosal to hematogenously disseminated candidiasis. The hyphal form plays an important role in the pathogenic process by invading epithelial cells and causing tissue damage. Notably, the secretion of the hyphal toxin candidalysin is essential for both epithelial cell damage and activation of mucosal immune responses. However, the mechanism of candidalysin-induced cell death remains unclear. Here, we examined the induction of cell death by candidalysin in oral epithelial cells. Fluorescent imaging using healthy/apoptotic/necrotic cell markers revealed that candidalysin causes a rapid and marked increase in the population of necrotic rather than apoptotic cells in a concentration dependent manner. Activation of a necrosis-like pathway was confirmed since C. albicans and candidalysin failed to activate caspase-8 and -3, or the cleavage of poly (ADP-ribose) polymerase. Furthermore, oral epithelial cells treated with candidalysin showed rapid production of reactive oxygen species, disruption of mitochondria activity and mitochondrial membrane potential, ATP depletion and cytochrome c release. Collectively, these data demonstrate that oral epithelial cells respond to the secreted fungal toxin candidalysin by triggering numerous cellular stress responses that induce necrotic death. TAKE AWAYS: Candidalysin secreted from Candida albicans causes epithelial cell stress. Candidalysin induces calcium influx and oxidative stress in host cells. Candidalysin induces mitochondrial dysfunction, ATP depletion and epithelial necrosis. The toxicity of candidalysin is mediated from the epithelial cell surface.

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 score0.005

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 integrity0.0000.001
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 head0.026
GPT teacher head0.256
Teacher spread0.230 · 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

Citations50
Published2021
Admission routes2
Has abstractyes

Explore more

Same venueCellular MicrobiologySame topicAntifungal resistance and susceptibilityFrench-language works237,207